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Conserved domains on  [gi|2462608991|ref|XP_054211656|]
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3-hydroxymethyl-3-methylglutaryl-CoA lyase, cytoplasmic isoform X2 [Homo sapiens]

Protein Classification

beta/alpha barrel domain-containing protein( domain architecture ID 229392)

beta/alpha barrel domain-containing protein belongs to a large superfamily with a wide variety of enzymatic functions

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
TIM super family cl21457
TIM-like beta/alpha barrel domains; A large family of domains similar to triose phosphate ...
 1-237 3.48e-142

TIM-like beta/alpha barrel domains; A large family of domains similar to triose phosphate isomerase (TIM) which, in general, share an eight beta/alpha closed barrel structure.


The actual alignment was detected with superfamily member PLN02746:

Pssm-ID: 473867  Cd Length: 347  Bit Score: 401.86  E-value: 3.48e-142
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462608991   1 MADHTEVMKGIHQYPGVRYPVLTPNLQGFHHAVAAGATEISVFGAASESFSKKNINCSIEESMGKFEEVVKSARHMNIPA 80
Cdd:PLN02746   99 LADAKDVMAAVRNLEGARFPVLTPNLKGFEAAIAAGAKEVAVFASASESFSKSNINCSIEESLVRYREVALAAKKHSIPV 178

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462608991  81 RGYVSCALGCPYEGSITPQKVTEVSKRLYGMGCYEISLGDTIGVGTPGSMKRMLESVMKEIPPGALAVHCHDTYGQALAN 160
Cdd:PLN02746  179 RGYVSCVVGCPIEGPVPPSKVAYVAKELYDMGCYEISLGDTIGVGTPGTVVPMLEAVMAVVPVDKLAVHFHDTYGQALAN 258

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2462608991 161 ILTALQMGINVVDSAVSGLGGCPYAKGASGNVATEDLIYMLNGLGLNTGVNLYKVMEAGDFICKAVNKTTNSKVAQA 237
Cdd:PLN02746  259 ILVSLQMGISTVDSSVAGLGGCPYAKGASGNVATEDVVYMLNGLGVSTNVDLGKLMAAGDFISKHLGRPSGSKTAVA 335
 
Name Accession Description Interval E-value
PLN02746 PLN02746
hydroxymethylglutaryl-CoA lyase
 1-237 3.48e-142

hydroxymethylglutaryl-CoA lyase


Pssm-ID: 178347  Cd Length: 347  Bit Score: 401.86  E-value: 3.48e-142
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462608991   1 MADHTEVMKGIHQYPGVRYPVLTPNLQGFHHAVAAGATEISVFGAASESFSKKNINCSIEESMGKFEEVVKSARHMNIPA 80
Cdd:PLN02746   99 LADAKDVMAAVRNLEGARFPVLTPNLKGFEAAIAAGAKEVAVFASASESFSKSNINCSIEESLVRYREVALAAKKHSIPV 178

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462608991  81 RGYVSCALGCPYEGSITPQKVTEVSKRLYGMGCYEISLGDTIGVGTPGSMKRMLESVMKEIPPGALAVHCHDTYGQALAN 160
Cdd:PLN02746  179 RGYVSCVVGCPIEGPVPPSKVAYVAKELYDMGCYEISLGDTIGVGTPGTVVPMLEAVMAVVPVDKLAVHFHDTYGQALAN 258

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2462608991 161 ILTALQMGINVVDSAVSGLGGCPYAKGASGNVATEDLIYMLNGLGLNTGVNLYKVMEAGDFICKAVNKTTNSKVAQA 237
Cdd:PLN02746  259 ILVSLQMGISTVDSSVAGLGGCPYAKGASGNVATEDVVYMLNGLGVSTNVDLGKLMAAGDFISKHLGRPSGSKTAVA 335
DRE_TIM_HMGL cd07938
3-hydroxy-3-methylglutaryl-CoA lyase, catalytic TIM barrel domain; ...
 1-224 4.86e-137

3-hydroxy-3-methylglutaryl-CoA lyase, catalytic TIM barrel domain; 3-hydroxy-3-methylglutaryl-CoA lyase (HMGL) catalyzes the cleavage of HMG-CoA to acetyl-CoA and acetoacetate, one of the terminal steps in ketone body generation and leucine degradation, and is a key enzyme in the pathway that supplies metabolic fuel to extrahepatic tissues. Mutations in HMGL cause a human autosomal recessive disorder called primary metabolic aciduria that affects ketogenesis and leucine catabolism and can be fatal due to an inability to tolerate hypoglycemia. HMGL has a TIM barrel domain with a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. The cleavage of HMG-CoA requires the presence of a divalent cation like Mg2+ or Mn2+, and the reaction is thought to involve general acid/base catalysis. This family belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".


Pssm-ID: 163676  Cd Length: 274  Bit Score: 385.59  E-value: 4.86e-137
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462608991   1 MADHTEVMKGIHQYPGVRYPVLTPNLQGFHHAVAAGATEISVFGAASESFSKKNINCSIEESMGKFEEVVKSARHMNIPA 80
Cdd:cd07938    51 MADAEEVLAGLPRRPGVRYSALVPNLRGAERALAAGVDEVAVFVSASETFSQKNINCSIAESLERFEPVAELAKAAGLRV 130

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462608991  81 RGYVSCALGCPYEGSITPQKVTEVSKRLYGMGCYEISLGDTIGVGTPGSMKRMLESVMKEIPPGALAVHCHDTYGQALAN 160
Cdd:cd07938   131 RGYVSTAFGCPYEGEVPPERVAEVAERLLDLGCDEISLGDTIGVATPAQVRRLLEAVLERFPDEKLALHFHDTRGQALAN 210

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2462608991 161 ILTALQMGINVVDSAVSGLGGCPYAKGASGNVATEDLIYMLNGLGLNTGVNLYKVMEAGDFICK 224
Cdd:cd07938   211 ILAALEAGVRRFDSSVGGLGGCPFAPGATGNVATEDLVYMLEGMGIETGIDLDKLLAAARWISE 274
HMGL-like pfam00682
HMGL-like; This family contains a diverse set of enzymes. These include various aldolases and ...
 3-222 7.54e-56

HMGL-like; This family contains a diverse set of enzymes. These include various aldolases and a region of pyruvate carboxylase.


Pssm-ID: 459902 [Multi-domain]  Cd Length: 264  Bit Score: 179.46  E-value: 7.54e-56
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462608991   3 DHTEVMKGIHQYPGVR--YPVLTPNLQGFHHAVA----AGATEISVFGAASESFSKKNINCSIEESMGKFEEVVKSARHM 76
Cdd:pfam00682  50 DDFEVVRAIAKVIPHAriLVLCRAREHDIKAAVEalkgAGAVRVHVFIATSDLHRKYKLGKDREEVAKRAVAAVKAARSR 129

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462608991  77 NIpargyvSCALGCPYEGSITPQKVTEVSKRLYGMGCYEISLGDTIGVGTPGSMKRMLESVMKEIPPGA-LAVHCHDTYG 155
Cdd:pfam00682 130 GI------DVEFSPEDASRTDPEFLAEVVEAAIEAGATRINIPDTVGVLTPNEAAELISALKARVPNKAiISVHCHNDLG 203

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2462608991 156 QALANILTALQMGINVVDSAVSGLGgcpyakGASGNVATEDLIYMLNGLGLNTGVNLYKVMEAGDFI 222
Cdd:pfam00682 204 MAVANSLAAVEAGADRVDGTVNGIG------ERAGNAALEEVAAALEGLGVDTGLDLQRLRSIANLV 264
LeuA COG0119
Isopropylmalate/homocitrate/citramalate synthases [Amino acid transport and metabolism]; ...
 33-231 4.60e-13

Isopropylmalate/homocitrate/citramalate synthases [Amino acid transport and metabolism]; Isopropylmalate/homocitrate/citramalate synthases is part of the Pathway/BioSystem: Isoleucine, leucine, valine biosynthesis


Pssm-ID: 439889 [Multi-domain]  Cd Length: 452  Bit Score: 67.88  E-value: 4.60e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462608991  33 VAAGATEISVFGAASESFSKKNINCSIEESMGKFEEVVKSARhmnipargyvscALGCPYE-----GSIT-PQKVTEVSK 106
Cdd:COG0119    88 KGAGVDRVHLFIKTSDLHVEYKLRKTREEVLEMAVEAVKYAK------------EHGLEVEfsaedATRTdPDFLLEVLE 155

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462608991 107 RLYGMGCYEISLGDTIGVGTPGSMKRMLESVMKEIPPGALAVHCHDTYGQALANILTALQMGINVVDSAVSGLGG-Cpya 185
Cdd:COG0119   156 AAIEAGADRINLPDTVGGATPNEVADLIEELRERVPDVILSVHCHNDLGLAVANSLAAVEAGADQVEGTINGIGErA--- 232

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*..
gi 2462608991 186 kgasGNVATEDLI-YMLNGLGLNTGVNLYKVMEagdfICKAVNKTTN 231
Cdd:COG0119   233 ----GNAALEEVVmNLKLKYGVDTGIDLSKLTE----LSRLVSEITG 271
 
Name Accession Description Interval E-value
PLN02746 PLN02746
hydroxymethylglutaryl-CoA lyase
 1-237 3.48e-142

hydroxymethylglutaryl-CoA lyase


Pssm-ID: 178347  Cd Length: 347  Bit Score: 401.86  E-value: 3.48e-142
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462608991   1 MADHTEVMKGIHQYPGVRYPVLTPNLQGFHHAVAAGATEISVFGAASESFSKKNINCSIEESMGKFEEVVKSARHMNIPA 80
Cdd:PLN02746   99 LADAKDVMAAVRNLEGARFPVLTPNLKGFEAAIAAGAKEVAVFASASESFSKSNINCSIEESLVRYREVALAAKKHSIPV 178

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462608991  81 RGYVSCALGCPYEGSITPQKVTEVSKRLYGMGCYEISLGDTIGVGTPGSMKRMLESVMKEIPPGALAVHCHDTYGQALAN 160
Cdd:PLN02746  179 RGYVSCVVGCPIEGPVPPSKVAYVAKELYDMGCYEISLGDTIGVGTPGTVVPMLEAVMAVVPVDKLAVHFHDTYGQALAN 258

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2462608991 161 ILTALQMGINVVDSAVSGLGGCPYAKGASGNVATEDLIYMLNGLGLNTGVNLYKVMEAGDFICKAVNKTTNSKVAQA 237
Cdd:PLN02746  259 ILVSLQMGISTVDSSVAGLGGCPYAKGASGNVATEDVVYMLNGLGVSTNVDLGKLMAAGDFISKHLGRPSGSKTAVA 335
DRE_TIM_HMGL cd07938
3-hydroxy-3-methylglutaryl-CoA lyase, catalytic TIM barrel domain; ...
 1-224 4.86e-137

3-hydroxy-3-methylglutaryl-CoA lyase, catalytic TIM barrel domain; 3-hydroxy-3-methylglutaryl-CoA lyase (HMGL) catalyzes the cleavage of HMG-CoA to acetyl-CoA and acetoacetate, one of the terminal steps in ketone body generation and leucine degradation, and is a key enzyme in the pathway that supplies metabolic fuel to extrahepatic tissues. Mutations in HMGL cause a human autosomal recessive disorder called primary metabolic aciduria that affects ketogenesis and leucine catabolism and can be fatal due to an inability to tolerate hypoglycemia. HMGL has a TIM barrel domain with a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. The cleavage of HMG-CoA requires the presence of a divalent cation like Mg2+ or Mn2+, and the reaction is thought to involve general acid/base catalysis. This family belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".


Pssm-ID: 163676  Cd Length: 274  Bit Score: 385.59  E-value: 4.86e-137
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462608991   1 MADHTEVMKGIHQYPGVRYPVLTPNLQGFHHAVAAGATEISVFGAASESFSKKNINCSIEESMGKFEEVVKSARHMNIPA 80
Cdd:cd07938    51 MADAEEVLAGLPRRPGVRYSALVPNLRGAERALAAGVDEVAVFVSASETFSQKNINCSIAESLERFEPVAELAKAAGLRV 130

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462608991  81 RGYVSCALGCPYEGSITPQKVTEVSKRLYGMGCYEISLGDTIGVGTPGSMKRMLESVMKEIPPGALAVHCHDTYGQALAN 160
Cdd:cd07938   131 RGYVSTAFGCPYEGEVPPERVAEVAERLLDLGCDEISLGDTIGVATPAQVRRLLEAVLERFPDEKLALHFHDTRGQALAN 210

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2462608991 161 ILTALQMGINVVDSAVSGLGGCPYAKGASGNVATEDLIYMLNGLGLNTGVNLYKVMEAGDFICK 224
Cdd:cd07938   211 ILAALEAGVRRFDSSVGGLGGCPFAPGATGNVATEDLVYMLEGMGIETGIDLDKLLAAARWISE 274
PRK05692 PRK05692
hydroxymethylglutaryl-CoA lyase; Provisional
 1-230 7.37e-137

hydroxymethylglutaryl-CoA lyase; Provisional


Pssm-ID: 180206  Cd Length: 287  Bit Score: 385.78  E-value: 7.37e-137
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462608991   1 MADHTEVMKGIHQYPGVRYPVLTPNLQGFHHAVAAGATEISVFGAASESFSKKNINCSIEESMGKFEEVVKSARHMNIPA 80
Cdd:PRK05692   57 MADAAEVMAGIQRRPGVTYAALTPNLKGLEAALAAGADEVAVFASASEAFSQKNINCSIAESLERFEPVAEAAKQAGVRV 136

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462608991  81 RGYVSCALGCPYEGSITPQKVTEVSKRLYGMGCYEISLGDTIGVGTPGSMKRMLESVMKEIPPGALAVHCHDTYGQALAN 160
Cdd:PRK05692  137 RGYVSCVLGCPYEGEVPPEAVADVAERLFALGCYEISLGDTIGVGTPGQVRAVLEAVLAEFPAERLAGHFHDTYGQALAN 216

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462608991 161 ILTALQMGINVVDSAVSGLGGCPYAKGASGNVATEDLIYMLNGLGLNTGVNLYKVMEAGDFICKAVNKTT 230
Cdd:PRK05692  217 IYASLEEGITVFDASVGGLGGCPYAPGASGNVATEDVLYMLHGLGIETGIDLDKLVRAGQFIQSKLGRPL 286
DRE_TIM_metallolyase cd03174
DRE-TIM metallolyase superfamily; The DRE-TIM metallolyase superfamily includes ...
 1-224 2.83e-80

DRE-TIM metallolyase superfamily; The DRE-TIM metallolyase superfamily includes 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".


Pssm-ID: 163674 [Multi-domain]  Cd Length: 265  Bit Score: 241.59  E-value: 2.83e-80
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462608991   1 MADHTEVMKGIHQY-PGVRYPVLTPN-LQGFHHAVAAGATEISVFGAASESFSKKNINCSIEESMGKFEEVVKSARHMNI 78
Cdd:cd03174    50 MEDDWEVLRAIRKLvPNVKLQALVRNrEKGIERALEAGVDEVRIFDSASETHSRKNLNKSREEDLENAEEAIEAAKEAGL 129

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462608991  79 PARGYVSCALGCPYegsiTPQKVTEVSKRLYGMGCYEISLGDTIGVGTPGSMKRMLESVMKEIPPGALAVHCHDTYGQAL 158
Cdd:cd03174   130 EVEGSLEDAFGCKT----DPEYVLEVAKALEEAGADEISLKDTVGLATPEEVAELVKALREALPDVPLGLHTHNTLGLAV 205

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2462608991 159 ANILTALQMGINVVDSAVSGLGgcpyakGASGNVATEDLIYMLNGLGLNTGVNLYKVMEAGDFICK 224
Cdd:cd03174   206 ANSLAALEAGADRVDGSVNGLG------ERAGNAATEDLVAALEGLGIDTGIDLEKLLEISRYVEE 265
HMGL-like pfam00682
HMGL-like; This family contains a diverse set of enzymes. These include various aldolases and ...
 3-222 7.54e-56

HMGL-like; This family contains a diverse set of enzymes. These include various aldolases and a region of pyruvate carboxylase.


Pssm-ID: 459902 [Multi-domain]  Cd Length: 264  Bit Score: 179.46  E-value: 7.54e-56
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462608991   3 DHTEVMKGIHQYPGVR--YPVLTPNLQGFHHAVA----AGATEISVFGAASESFSKKNINCSIEESMGKFEEVVKSARHM 76
Cdd:pfam00682  50 DDFEVVRAIAKVIPHAriLVLCRAREHDIKAAVEalkgAGAVRVHVFIATSDLHRKYKLGKDREEVAKRAVAAVKAARSR 129

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462608991  77 NIpargyvSCALGCPYEGSITPQKVTEVSKRLYGMGCYEISLGDTIGVGTPGSMKRMLESVMKEIPPGA-LAVHCHDTYG 155
Cdd:pfam00682 130 GI------DVEFSPEDASRTDPEFLAEVVEAAIEAGATRINIPDTVGVLTPNEAAELISALKARVPNKAiISVHCHNDLG 203

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2462608991 156 QALANILTALQMGINVVDSAVSGLGgcpyakGASGNVATEDLIYMLNGLGLNTGVNLYKVMEAGDFI 222
Cdd:pfam00682 204 MAVANSLAAVEAGADRVDGTVNGIG------ERAGNAALEEVAAALEGLGVDTGLDLQRLRSIANLV 264
DRE_TIM_HOA cd07943
4-hydroxy-2-oxovalerate aldolase, N-terminal catalytic TIM barrel domain; 4-hydroxy ...
 96-222 4.02e-15

4-hydroxy-2-oxovalerate aldolase, N-terminal catalytic TIM barrel domain; 4-hydroxy 2-ketovalerate aldolase (Also known as 4-hydroxy-2-ketovalerate aldolase and 4-hydroxy-2-oxopentanoate aldolase (HOA)) converts 4-hydroxy-2-oxopentanoate to acetaldehyde and pyruvate, the penultimate step in the meta-cleavage pathway for the degradation of phenols, cresols and catechol. This family includes the Escherichia coli MhpE aldolase, the Pseudomonas DmpG aldolase, and the Burkholderia xenovorans BphI pyruvate aldolase. In Pseudomonas, the DmpG aldolase tightly associates with a dehydrogenase (DmpF ) and is inactive without it. HOA has a canonical TIM-barrel fold with a C-terminal extension that forms a funnel leading to the active site. This family belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".


Pssm-ID: 163681  Cd Length: 263  Bit Score: 72.53  E-value: 4.02e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462608991  96 ITPQKVTEVSKRLYGMGCYEISLGDTIGVGTPGSMKRMLESVMKEIPPGALAVHCHDTYGQALANILTALQMGINVVDSA 175
Cdd:cd07943   138 ASPEELAEQAKLMESYGADCVYVTDSAGAMLPDDVRERVRALREALDPTPVGFHGHNNLGLAVANSLAAVEAGATRIDGS 217

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 2462608991 176 VSGLGGCpyakgaSGNVATEDLIYMLNGLGLNTGVNLYKVMEAGDFI 222
Cdd:cd07943   218 LAGLGAG------AGNTPLEVLVAVLERMGIETGIDLYKLMDAAEDL 258
DRE_TIM_HOA_like cd07944
4-hydroxy-2-oxovalerate aldolase-like, N-terminal catalytic TIM barrel domain; This family of ...
 65-218 3.04e-14

4-hydroxy-2-oxovalerate aldolase-like, N-terminal catalytic TIM barrel domain; This family of bacterial enzymes is sequence-similar to 4-hydroxy-2-oxovalerate aldolase (HOA) but its exact function is unknown. This family includes the Bacteroides vulgatus Bvu_2661 protein and belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".


Pssm-ID: 163682  Cd Length: 266  Bit Score: 69.90  E-value: 3.04e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462608991  65 KFEEVVKSARHmnIPARGY-VSCALgcPYEGSITPQKVTEVSKRLYGMGCYEISLGDTIGVGTPGSMKRMLESVMKEIPP 143
Cdd:cd07944   107 EFDEALPLIKA--IKEKGYeVFFNL--MAISGYSDEELLELLELVNEIKPDVFYIVDSFGSMYPEDIKRIISLLRSNLDK 182

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2462608991 144 G-ALAVHCHDTYGQALANILTALQMGINVVDSAVSGLGgcpyaKGAsGNVATEDLIYMLNGLgLNTGVNLYKVMEA 218
Cdd:cd07944   183 DiKLGFHAHNNLQLALANTLEAIELGVEIIDATVYGMG-----RGA-GNLPTELLLDYLNNK-FGKKYNLEPVLEL 251
DRE_TIM_PC_TC_5S cd07937
Pyruvate carboxylase and Transcarboxylase 5S, carboxyltransferase domain; This family includes ...
 97-228 5.40e-14

Pyruvate carboxylase and Transcarboxylase 5S, carboxyltransferase domain; This family includes the carboxyltransferase domains of pyruvate carboxylase (PC) and the transcarboxylase (TC) 5S subunit. Transcarboxylase 5S is a cobalt-dependent metalloenzyme subunit of the biotin-dependent transcarboxylase multienzyme complex. Transcarboxylase 5S transfers carbon dioxide from the 1.3S biotin to pyruvate in the second of two carboxylation reactions catalyzed by TC. The first reaction involves the transfer of carbon dioxide from methylmalonyl-CoA to the 1.3S biotin, and is catalyzed by the 12S subunit. These two steps allow a carboxylate group to be transferred from oxaloacetate to propionyl-CoA to yield pyruvate and methylmalonyl-CoA. The catalytic domain of transcarboxylase 5S has a canonical TIM-barrel fold with a large C-terminal extension that forms a funnel leading to the active site. Transcarboxylase 5S forms a homodimer and there are six dimers per complex. In addition to the catalytic domain, transcarboxylase 5S has several other domains including a carbamoyl-phosphate synthase domain, a biotin carboxylase domain, a carboxyltransferase domain, and an ATP-grasp domain. Pyruvate carboxylase, like TC, is a biotin-dependent enzyme that catalyzes the carboxylation of pyruvate to produce oxaloacetate. In mammals, PC has critical roles in gluconeogenesis, lipogenesis, glyceroneogenesis, and insulin secretion. Inherited PC deficiencies are linked to serious diseases in humans such as lactic acidemia, hypoglycemia, psychomotor retardation, and death. PC is a single-chain enzyme and is active only in its homotetrameric form. PC has three domains, an N-terminal biotin carboxylase domain, a carboxyltransferase domain (this alignment model), and a C-terminal biotin-carboxyl carrier protein domain. This family belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".


Pssm-ID: 163675  Cd Length: 275  Bit Score: 69.38  E-value: 5.40e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462608991  97 TPQKVTEVSKRLYGMGCYEISLGDTIGVGTPGSMKRMLESVMKEIP-PgaLAVHCHDTYGQALANILTALQMGINVVDSA 175
Cdd:cd07937   147 TLEYYVKLAKELEDMGADSICIKDMAGLLTPYAAYELVKALKKEVGlP--IHLHTHDTSGLAVATYLAAAEAGVDIVDTA 224

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 2462608991 176 VSGLGGCpyakgaSGNVATEDLIYMLNGLGLNTGVNLYKVMEAGDfICKAVNK 228
Cdd:cd07937   225 ISPLSGG------TSQPSTESMVAALRGTGRDTGLDLEKLEEISE-YFEEVRK 270
LeuA COG0119
Isopropylmalate/homocitrate/citramalate synthases [Amino acid transport and metabolism]; ...
 33-231 4.60e-13

Isopropylmalate/homocitrate/citramalate synthases [Amino acid transport and metabolism]; Isopropylmalate/homocitrate/citramalate synthases is part of the Pathway/BioSystem: Isoleucine, leucine, valine biosynthesis


Pssm-ID: 439889 [Multi-domain]  Cd Length: 452  Bit Score: 67.88  E-value: 4.60e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462608991  33 VAAGATEISVFGAASESFSKKNINCSIEESMGKFEEVVKSARhmnipargyvscALGCPYE-----GSIT-PQKVTEVSK 106
Cdd:COG0119    88 KGAGVDRVHLFIKTSDLHVEYKLRKTREEVLEMAVEAVKYAK------------EHGLEVEfsaedATRTdPDFLLEVLE 155

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462608991 107 RLYGMGCYEISLGDTIGVGTPGSMKRMLESVMKEIPPGALAVHCHDTYGQALANILTALQMGINVVDSAVSGLGG-Cpya 185
Cdd:COG0119   156 AAIEAGADRINLPDTVGGATPNEVADLIEELRERVPDVILSVHCHNDLGLAVANSLAAVEAGADQVEGTINGIGErA--- 232

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*..
gi 2462608991 186 kgasGNVATEDLI-YMLNGLGLNTGVNLYKVMEagdfICKAVNKTTN 231
Cdd:COG0119   233 ----GNAALEEVVmNLKLKYGVDTGIDLSKLTE----LSRLVSEITG 271
DRE_TIM_IPMS cd07940
2-isopropylmalate synthase (IPMS), N-terminal catalytic TIM barrel domain; 2-isopropylmalate ...
 112-224 1.17e-12

2-isopropylmalate synthase (IPMS), N-terminal catalytic TIM barrel domain; 2-isopropylmalate synthase (IPMS) catalyzes an aldol-type condensation of acetyl-CoA and 2-oxoisovalerate yielding 2-isopropylmalate and CoA, the first committed step in leucine biosynthesis. This family includes the Arabidopsis thaliana IPMS1 and IPMS2 proteins, the Glycine max GmN56 protein, and the Brassica insularis BatIMS protein. This family also includes a group of archeal IPMS-like proteins represented by the Methanocaldococcus jannaschii AksA protein. AksA catalyzes the condensation of alpha-ketoglutarate and acetyl-CoA to form trans-homoaconitate, one of 13 steps in the conversion of alpha-ketoglutarate and acetylCoA to alpha-ketosuberate, a precursor to coenzyme B and biotin. AksA also catalyzes the condensation of alpha-ketoadipate or alpha-ketopimelate with acetylCoA to form, respectively, the (R)-homocitrate homologs (R)-2-hydroxy-1,2,5-pentanetricarboxylic acid and (R)-2-hydroxy-1,2,6- hexanetricarboxylic acid. This family belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".


Pssm-ID: 163678  Cd Length: 268  Bit Score: 65.55  E-value: 1.17e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462608991 112 GCYEISLGDTIGVGTPGSMKRMLESVMKEIPPGA--LAVHCHDTYGQALANILTALQMGINVVDSAVSGLGgcpyakGAS 189
Cdd:cd07940   156 GATTINIPDTVGYLTPEEFGELIKKLKENVPNIKvpISVHCHNDLGLAVANSLAAVEAGARQVECTINGIG------ERA 229

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 2462608991 190 GNVATEDLI----YMLNGLGLNTGVNLYKVMEAGDFICK 224
Cdd:cd07940   230 GNAALEEVVmalkTRYDYYGVETGIDTEELYETSRLVSR 268
PRK09282 PRK09282
pyruvate carboxylase subunit B; Validated
 97-228 4.97e-12

pyruvate carboxylase subunit B; Validated


Pssm-ID: 236449 [Multi-domain]  Cd Length: 592  Bit Score: 64.86  E-value: 4.97e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462608991  97 TPQKVTEVSKRLYGMGCYEISLGDTIGVGTPGSMKRmLESVMKE---IPpgaLAVHCHDTYGQALANILTALQMGINVVD 173
Cdd:PRK09282  152 TIEKYVELAKELEEMGCDSICIKDMAGLLTPYAAYE-LVKALKEevdLP---VQLHSHCTSGLAPMTYLKAVEAGVDIID 227

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 2462608991 174 SAVSglggcPYAKGASgNVATEDLIYMLNGLGLNTGVNLYKVMEAGDfICKAVNK 228
Cdd:PRK09282  228 TAIS-----PLAFGTS-QPPTESMVAALKGTPYDTGLDLELLFEIAE-YFREVRK 275
PRK08195 PRK08195
4-hyroxy-2-oxovalerate/4-hydroxy-2-oxopentanoic acid aldolase,; Validated
 96-220 7.10e-11

4-hyroxy-2-oxovalerate/4-hydroxy-2-oxopentanoic acid aldolase,; Validated


Pssm-ID: 181282 [Multi-domain]  Cd Length: 337  Bit Score: 61.00  E-value: 7.10e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462608991  96 ITPQKVTEVSKRLYGMGCYEISLGDTIGVGTPGSMKRMLESVMKEIPPGA-LAVHCHDTYGQALANILTALQMGINVVDS 174
Cdd:PRK08195  141 APPEKLAEQAKLMESYGAQCVYVVDSAGALLPEDVRDRVRALRAALKPDTqVGFHGHNNLGLGVANSLAAVEAGATRIDG 220

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 2462608991 175 AVSGLGGcpyakGAsGNVATEDLIYMLNGLGLNTGVNLYKVMEAGD 220
Cdd:PRK08195  221 SLAGLGA-----GA-GNTPLEVLVAVLDRMGWETGVDLYKLMDAAE 260
aksA PRK11858
trans-homoaconitate synthase; Reviewed
 111-235 1.32e-10

trans-homoaconitate synthase; Reviewed


Pssm-ID: 183341 [Multi-domain]  Cd Length: 378  Bit Score: 60.19  E-value: 1.32e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462608991 111 MGCYEISLGDTIGVGTPGSM----KRMLESVMKEIppgalAVHCHDTYGQALANILTALQMGINVVDSAVSGLGgcpyak 186
Cdd:PRK11858  157 AGADRVRFCDTVGILDPFTMyelvKELVEAVDIPI-----EVHCHNDFGMATANALAGIEAGAKQVHTTVNGLG------ 225

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 2462608991 187 GASGNVATEDLIYMLNGL-GLNTGVNLYKVMEagdfICKAVNKTTNSKVA 235
Cdd:PRK11858  226 ERAGNAALEEVVMALKYLyGIDLGIDTERLYE----LSRLVSKASGIPVP 271
PRK12331 PRK12331
oxaloacetate decarboxylase subunit alpha;
103-221 1.48e-10

oxaloacetate decarboxylase subunit alpha;


Pssm-ID: 183446 [Multi-domain]  Cd Length: 448  Bit Score: 60.49  E-value: 1.48e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462608991 103 EVSKRLYGMGCYEISLGDTIGVGTPGS----MKRMLESVmkEIPpgaLAVHCHDTYGQALANILTALQMGINVVDSAVSg 178
Cdd:PRK12331  158 KLAKEMQEMGADSICIKDMAGILTPYVayelVKRIKEAV--TVP---LEVHTHATSGIAEMTYLKAIEAGADIIDTAIS- 231

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 2462608991 179 lggcPYAKGASgNVATEDLIYMLNGLGLNTGVNLYKVMEAGDF 221
Cdd:PRK12331  232 ----PFAGGTS-QPATESMVAALQDLGYDTGLDLEELSEIAEY 269
PRK14040 PRK14040
oxaloacetate decarboxylase subunit alpha;
66-217 1.52e-10

oxaloacetate decarboxylase subunit alpha;


Pssm-ID: 237592 [Multi-domain]  Cd Length: 593  Bit Score: 60.33  E-value: 1.52e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462608991  66 FEEVVKSARHMNIPARGYVScalgcpYEGSI--TPQKVTEVSKRLYGMGCYEISLGDTIGVGTPGS----MKRMLESVmk 139
Cdd:PRK14040  126 LETALKAVRKVGAHAQGTLS------YTTSPvhTLQTWVDLAKQLEDMGVDSLCIKDMAGLLKPYAayelVSRIKKRV-- 197

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2462608991 140 EIPpgaLAVHCHDTYGQALANILTALQMGINVVDSAVSGLgGCPYakgasGNVATEDLIYMLNGLGLNTGVNLYKVME 217
Cdd:PRK14040  198 DVP---LHLHCHATTGLSTATLLKAIEAGIDGVDTAISSM-SMTY-----GHSATETLVATLEGTERDTGLDILKLEE 266
PRK12330 PRK12330
methylmalonyl-CoA carboxytransferase subunit 5S;
97-220 1.83e-10

methylmalonyl-CoA carboxytransferase subunit 5S;


Pssm-ID: 183445 [Multi-domain]  Cd Length: 499  Bit Score: 60.16  E-value: 1.83e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462608991  97 TPQKVTEVSKRLYGMGCYEISLGDTIGVGTPGSMKRMLESVMKEIPPGA-LAVHCHDTYGQALANILTALQMGINVVDSA 175
Cdd:PRK12330  153 TVEGFVEQAKRLLDMGADSICIKDMAALLKPQPAYDIVKGIKEACGEDTrINLHCHSTTGVTLVSLMKAIEAGVDVVDTA 232

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 2462608991 176 VSGLGGCPyakgasGNVATEDLIYMLNGLGLNTGVNLYKVMEAGD 220
Cdd:PRK12330  233 ISSMSLGP------GHNPTESLVEMLEGTGYTTKLDMDRLLKIRD 271
PRK09389 PRK09389
(R)-citramalate synthase; Provisional
 106-235 1.68e-09

(R)-citramalate synthase; Provisional


Pssm-ID: 236493 [Multi-domain]  Cd Length: 488  Bit Score: 57.26  E-value: 1.68e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462608991 106 KRLYGMGcyeISLG-------DTIGVGTPgsmKRMLESV--MKEIPPGALAVHCHDTYGQALANILTALQMGINVVDSAV 176
Cdd:PRK09389  146 KELYKAG---IEAGadricfcDTVGILTP---EKTYELFkrLSELVKGPVSIHCHNDFGLAVANTLAALAAGADQVHVTI 219

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462608991 177 SGLGgcpyakGASGNVATEDLIYMLNGL-GLNTGVNLYKVMEagdfICKAVNKTTNSKVA 235
Cdd:PRK09389  220 NGIG------ERAGNASLEEVVMALKHLyDVETGIKLEELYE----LSRLVSRLTGIPVP 269
PRK00915 PRK00915
2-isopropylmalate synthase; Validated
 66-234 3.99e-09

2-isopropylmalate synthase; Validated


Pssm-ID: 234864 [Multi-domain]  Cd Length: 513  Bit Score: 56.27  E-value: 3.99e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462608991  66 FEEVVKSARHMNIPARGYV-----SCalgcpyE-GSIT-PQKVTEVSKRLYGMGCYEISLGDTIGVGTPGSMKRMLESVM 138
Cdd:PRK00915  115 REEVLEMAVEAVKYARSYTddvefSA------EdATRTdLDFLCRVVEAAIDAGATTINIPDTVGYTTPEEFGELIKTLR 188

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462608991 139 KEIPPGALA---VHCHDTYGQALANILTALQMGINVVDSAVSGLGgcpyaKGAsGNVATEDLIYMLN----GLGLNTGVN 211
Cdd:PRK00915  189 ERVPNIDKAiisVHCHNDLGLAVANSLAAVEAGARQVECTINGIG-----ERA-GNAALEEVVMALKtrkdIYGVETGIN 262

                         170       180
                  ....*....|....*....|...
gi 2462608991 212 LYKVMEAgdfiCKAVNKTTNSKV 234
Cdd:PRK00915  263 TEEIYRT----SRLVSQLTGMPV 281
PLN03228 PLN03228
methylthioalkylmalate synthase; Provisional
 40-216 6.98e-08

methylthioalkylmalate synthase; Provisional


Pssm-ID: 178767 [Multi-domain]  Cd Length: 503  Bit Score: 52.62  E-value: 6.98e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462608991  40 ISVFGAASESFSKKNINCSIEESMGKFEEVVKSARHMniparGYVSCALGCPYEGSITPQKVTEVSKRLYGMGCYEISLG 119
Cdd:PLN03228  185 ILAFTSTSDIHMKYKLKKTKEEVIEMAVSSIRYAKSL-----GFHDIQFGCEDGGRSDKEFLCKILGEAIKAGATSVGIA 259

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462608991 120 DTIGVGTPGSMKRMLESVmKEIPPGA----LAVHCHDTYGQALANILTALQMGINVVDSAVSGLGgcpyakGASGNVATE 195
Cdd:PLN03228  260 DTVGINMPHEFGELVTYV-KANTPGIddivFSVHCHNDLGLATANTIAGICAGARQVEVTINGIG------ERSGNASLE 332

                         170       180
                  ....*....|....*....|....*....
gi 2462608991 196 DLI--------YMLNglGLNTGVNLYKVM 216
Cdd:PLN03228  333 EVVmalkcrgaYLMN--GVYTGIDTRQIM 359
DRE_TIM_CMS cd07945
Leptospira interrogans citramalate synthase (CMS) and related proteins, N-terminal catalytic ...
 116-211 1.51e-06

Leptospira interrogans citramalate synthase (CMS) and related proteins, N-terminal catalytic TIM barrel domain; Citramalate synthase (CMS) catalyzes the conversion of pyruvate and acetyl-CoA to (R)-citramalate in the first dedicated step of the citramalate pathway. Citramalate is only found in Leptospira interrogans and a few other microorganisms. This family belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".


Pssm-ID: 163683 [Multi-domain]  Cd Length: 280  Bit Score: 48.14  E-value: 1.51e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462608991 116 ISLGDTIGVGTPGSMKRMLESVMKEIPPGALAVHCHDTYGQALANILTALQMGINVVDSAVSGLGgcpyakGASGNVATE 195
Cdd:cd07945   164 IMLPDTLGILSPFETYTYISDMVKRYPNLHFDFHAHNDYDLAVANVLAAVKAGIKGLHTTVNGLG------ERAGNAPLA 237

                          90
                  ....*....|....*..
gi 2462608991 196 DLIYMLNG-LGLNTGVN 211
Cdd:cd07945   238 SVIAVLKDkLKVKTNID 254
DRE_TIM_Re_CS cd07947
Clostridium kluyveri Re-citrate synthase and related proteins, catalytic TIM barrel domain; ...
 52-222 1.73e-06

Clostridium kluyveri Re-citrate synthase and related proteins, catalytic TIM barrel domain; Re-citrate synthase (Re-CS) is a Clostridium kluyveri enzyme that converts acetyl-CoA and oxaloacetate to citrate. In most organisms, this reaction is catalyzed by Si-citrate synthase which is Si-face stereospecific with respect to C-2 of oxaloacetate, and phylogenetically unrelated to Re-citrate synthase. Re-citrate synthase is also found in a few other strictly anaerobic organisms. This family belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".


Pssm-ID: 163684  Cd Length: 279  Bit Score: 47.70  E-value: 1.73e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462608991  52 KKNINCSIEESMGKFEEVVKSARHMNIPARgyvsCALG----CPYEGSITP--QKVTEVSKRlYGMGCYeISLGDTIGVG 125
Cdd:cd07947   103 FKKLKMTREEAMEKYLEIVEEALDHGIKPR----CHLEditrADIYGFVLPfvNKLMKLSKE-SGIPVK-IRLCDTLGYG 176

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462608991 126 T-------PGSMKRMLESVMKE--IPPGALAVHCHDTYGQALANILTALQMGINVVDSAVSGLGgcpyakGASGNVATED 196
Cdd:cd07947   177 VpypgaslPRSVPKIIYGLRKDcgVPSENLEWHGHNDFYKAVANAVAAWLYGASWVNCTLLGIG------ERTGNCPLEA 250

                         170       180
                  ....*....|....*....|....*..
gi 2462608991 197 LIYMLNGLGLNT-GVNLYKVMEAGDFI 222
Cdd:cd07947   251 MVIEYAQLKGNFdGMNLEVITEIAEYF 277
PRK14042 PRK14042
pyruvate carboxylase subunit B; Provisional
 103-228 3.82e-06

pyruvate carboxylase subunit B; Provisional


Pssm-ID: 172536 [Multi-domain]  Cd Length: 596  Bit Score: 47.41  E-value: 3.82e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462608991 103 EVSKRLYGMGCYEISLGDTIGVGTPgSMKRMLESVMKEIPPGALAVHCHDTYGQALANILTALQMGINVVDSAVSGLGGc 182
Cdd:PRK14042  158 ELGKKLAEMGCDSIAIKDMAGLLTP-TVTVELYAGLKQATGLPVHLHSHSTSGLASICHYEAVLAGCNHIDTAISSFSG- 235

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 2462608991 183 pyakGASgNVATEDLIYMLNGLGLNTGVNLYKVMEAGDFIcKAVNK 228
Cdd:PRK14042  236 ----GAS-HPPTEALVAALTDTPYDTELDLNILLEIDDYF-KAVRK 275
DRE_TIM_LeuA3 cd07941
Desulfobacterium autotrophicum LeuA3 and related proteins, N-terminal catalytic TIM barrel ...
 116-180 4.47e-06

Desulfobacterium autotrophicum LeuA3 and related proteins, N-terminal catalytic TIM barrel domain; Desulfobacterium autotrophicum LeuA3 is sequence-similar to alpha-isopropylmalate synthase (LeuA) but its exact function is unknown. Members of this family have an N-terminal TIM barrel domain that belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".


Pssm-ID: 163679  Cd Length: 273  Bit Score: 46.68  E-value: 4.47e-06
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2462608991 116 ISLGDTIGvGT-PGSMKRMLESVMKEIPPGALAVHCHDTYGQALANILTALQMGINVVDSAVSGLG 180
Cdd:cd07941   168 LVLCDTNG-GTlPHEIAEIVKEVRERLPGVPLGIHAHNDSGLAVANSLAAVEAGATQVQGTINGYG 232
PRK12581 PRK12581
oxaloacetate decarboxylase; Provisional
 106-228 7.12e-06

oxaloacetate decarboxylase; Provisional


Pssm-ID: 79056 [Multi-domain]  Cd Length: 468  Bit Score: 46.26  E-value: 7.12e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462608991 106 KRLYGMGCYEISLGDTIGVGTPGSMKRMLESV--MKEIPpgaLAVHCHDTYGQALANILTALQMGINVVDSAVSglggcP 183
Cdd:PRK12581  170 KELVEMGADSICIKDMAGILTPKAAKELVSGIkaMTNLP---LIVHTHATSGISQMTYLAAVEAGADRIDTALS-----P 241

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 2462608991 184 YAKGASgNVATEDLIYMLNGLGLNTGVNLYKVMEAGDFICKAVNK 228
Cdd:PRK12581  242 FSEGTS-QPATESMYLALKEAGYDITLDETLLEQAANHLRQARQK 285
DRE_TIM_NifV cd07939
Streptomyces rubellomurinus FrbC and related proteins, catalytic TIM barrel domain; FrbC (NifV) ...
 120-180 2.09e-05

Streptomyces rubellomurinus FrbC and related proteins, catalytic TIM barrel domain; FrbC (NifV) of Streptomyces rubellomurinus catalyzes the condensation of acetyl-CoA and alpha-ketoglutarate to form homocitrate and CoA, a reaction similar to one catalyzed by homocitrate synthase. The gene encoding FrbC is one of several genes required for the biosynthesis of FR900098, a potent antimalarial antibiotic. This protein is also required for assembly of the nitrogenase MoFe complex but its exact role is unknown. This family also includes the NifV proteins of Heliobacterium chlorum and Gluconacetobacter diazotrophicus, which appear to be orthologous to FrbC. This family belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".


Pssm-ID: 163677 [Multi-domain]  Cd Length: 259  Bit Score: 44.42  E-value: 2.09e-05
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2462608991 120 DTIGVGTPGSMKRMLESVMKEIPpGALAVHCHDTYGQALANILTALQMGINVVDSAVSGLG 180
Cdd:cd07939   160 DTVGILDPFTTYELIRRLRAATD-LPLEFHAHNDLGLATANTLAAVRAGATHVSVTVNGLG 219
DRE_TIM_HCS cd07948
Saccharomyces cerevisiae homocitrate synthase and related proteins, catalytic TIM barrel ...
 111-180 1.09e-04

Saccharomyces cerevisiae homocitrate synthase and related proteins, catalytic TIM barrel domain; Homocitrate synthase (HCS) catalyzes the condensation of acetyl-CoA and alpha-ketoglutarate to form homocitrate, the first step in the lysine biosynthesis pathway. This family includes the Yarrowia lipolytica LYS1 protein as well as the Saccharomyces cerevisiae LYS20 and LYS21 proteins. This family belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".


Pssm-ID: 163685  Cd Length: 262  Bit Score: 42.32  E-value: 1.09e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462608991 111 MGCYEISLGDTIGVGTPGSMKRMLESVMKEIPPGaLAVHCHDTYGQALANILTALQMGINVVDSAVSGLG 180
Cdd:cd07948   153 LGVNRVGIADTVGIATPRQVYELVRTLRGVVSCD-IEFHGHNDTGCAIANAYAALEAGATHIDTTVLGIG 221
PRK12999 PRK12999
pyruvate carboxylase; Reviewed
 148-226 1.08e-03

pyruvate carboxylase; Reviewed


Pssm-ID: 237263 [Multi-domain]  Cd Length: 1146  Bit Score: 40.12  E-value: 1.08e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462608991  148 VHCHDTYGQALANILTALQMGINVVDSAVSGLGGcpyakGAS-GNVATedLIYMLNGLGLNTGVNLYKVMEAGDFiCKAV 226
Cdd:PRK12999   739 LHTHDTSGNGLATYLAAAEAGVDIVDVAVASMSG-----LTSqPSLNS--IVAALEGTERDTGLDLDAIRKLSPY-WEAV 810
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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