Isopentenyl diphosphate isomerase; Isopentenyl diphosphate (IPP) isomerase, a member of the NUDIX hydrolase superfamily, is a key enzyme in the isoprenoid biosynthetic pathway. Isoprenoids comprise a large family of natural products including sterols, carotenoids, dolichols and prenylated proteins. These compounds are synthesized from two precursors: isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). IPP isomerase catalyzes the interconversion of IPP and DMAPP by a stereoselective antarafacial transposition of hydrogen. The enzyme requires one Mn2+ or Mg2+ ion in its active site to fold into an active conformation and also contains the NUDIX motif, a highly conserved 23-residue block (GX5EX7REUXEEXGU, where U = I, L or V), that functions as a metal binding and catalytic site. The metal binding site is present within the active site and plays structural and catalytical roles. IPP isomerase is well represented in several bacteria, archaebacteria and eukaryotes, including fungi, mammals and plants. Despite sequence variations (mainly at the N-terminus), the core structure is highly conserved.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 964749142  16 LLHGLLHRAFSVFLFNTENKLLLQQRSDAKITFPGCFTNTCCSHPLsnPAEleesdalGVRRAAQRRLKAELGIpleevP 95
Cdd:cd02885   22 RKGTLLHRAFSVFLFNSKGELLLQRRALSKYTWPGLWTNTCCSHPL--PGE-------GVEDAAQRRLREELGI-----P 87

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 964749142  96 PEEINYLTRIHYKAQSDGIWGEHEIDYILLVRKNVTLNPDPNEIKSYCYVSkeeLKELLKKAASGEIKITPWFKIIAA 173
Cdd:cd02885   88 VCDLEELPRFRYRATDDNGLVEHEIDHVFVGRADGDPVPNPEEVSDYRWVS---LEELRELLAATPEAFTPWFRLILE 162

Isopentenyldiphosphate isomerase [Lipid transport and metabolism]; Isopentenyldiphosphate isomerase is part of the Pathway/BioSystem: Isoprenoid biosynthesis

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 964749142  19 GLLHRAFSVFLFNTENKLLLQQRSDAKITFPGCFTNTCCSHPLSNpaeleESdalgVRRAAQRRLKAELGIpleeVPPEE 98
Cdd:COG1443   26 GLLHRAFSVFVFNSDGRLLLQRRALTKDHWPGLWDNTVCGHPRAG-----ET----YEEAAVRELEEELGI----TVDDD 92

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 964749142  99 INYLTRIHYKAQSDGIWGEHEIDYILLVRKNVTLNPDPNEIKSYCYVSkeeLKELLKKAASGEIKITPWFKII 171
Cdd:COG1443   93 LRPLGTFRYRAVDANGLVENEFCHVFVARLDGPLTPQPEEVAEVRWVT---LEELLALLEAGPEAFTPWFRLY 162

Isopentenyl diphosphate isomerase; Isopentenyl diphosphate (IPP) isomerase, a member of the NUDIX hydrolase superfamily, is a key enzyme in the isoprenoid biosynthetic pathway. Isoprenoids comprise a large family of natural products including sterols, carotenoids, dolichols and prenylated proteins. These compounds are synthesized from two precursors: isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). IPP isomerase catalyzes the interconversion of IPP and DMAPP by a stereoselective antarafacial transposition of hydrogen. The enzyme requires one Mn2+ or Mg2+ ion in its active site to fold into an active conformation and also contains the NUDIX motif, a highly conserved 23-residue block (GX5EX7REUXEEXGU, where U = I, L or V), that functions as a metal binding and catalytic site. The metal binding site is present within the active site and plays structural and catalytical roles. IPP isomerase is well represented in several bacteria, archaebacteria and eukaryotes, including fungi, mammals and plants. Despite sequence variations (mainly at the N-terminus), the core structure is highly conserved.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 964749142  16 LLHGLLHRAFSVFLFNTENKLLLQQRSDAKITFPGCFTNTCCSHPLsnPAEleesdalGVRRAAQRRLKAELGIpleevP 95
Cdd:cd02885   22 RKGTLLHRAFSVFLFNSKGELLLQRRALSKYTWPGLWTNTCCSHPL--PGE-------GVEDAAQRRLREELGI-----P 87

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 964749142  96 PEEINYLTRIHYKAQSDGIWGEHEIDYILLVRKNVTLNPDPNEIKSYCYVSkeeLKELLKKAASGEIKITPWFKIIAA 173
Cdd:cd02885   88 VCDLEELPRFRYRATDDNGLVEHEIDHVFVGRADGDPVPNPEEVSDYRWVS---LEELRELLAATPEAFTPWFRLILE 162

Isopentenyldiphosphate isomerase [Lipid transport and metabolism]; Isopentenyldiphosphate isomerase is part of the Pathway/BioSystem: Isoprenoid biosynthesis

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 964749142  19 GLLHRAFSVFLFNTENKLLLQQRSDAKITFPGCFTNTCCSHPLSNpaeleESdalgVRRAAQRRLKAELGIpleeVPPEE 98
Cdd:COG1443   26 GLLHRAFSVFVFNSDGRLLLQRRALTKDHWPGLWDNTVCGHPRAG-----ET----YEEAAVRELEEELGI----TVDDD 92

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 964749142  99 INYLTRIHYKAQSDGIWGEHEIDYILLVRKNVTLNPDPNEIKSYCYVSkeeLKELLKKAASGEIKITPWFKII 171
Cdd:COG1443   93 LRPLGTFRYRAVDANGLVENEFCHVFVARLDGPLTPQPEEVAEVRWVT---LEELLALLEAGPEAFTPWFRLY 162

uncharacterized NUDIX hydrolase subfamily; NUDIX hydrolase is a superfamily of enzymes found in all three kingdoms of life, and it catalyzes the hydrolysis of NUcleoside DIphosphates linked to other moieties, X. Enzymes belonging to this superfamily require a divalent cation, such as Mg2+ or Mn2+ for their activity. Members of this family are recognized by a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V), which forms a structural motif that functions as a metal binding and catalytic site. Substrates of NUDIX hydrolase include intact and oxidatively damaged nucleoside triphosphates, dinucleoside polyphosphates, nucleotide-sugars and dinucleotide enzymes. These substrates are metabolites or cell signaling molecules that require regulation during different stages of the cell cycle or during periods of stress. In general, the role of the NUDIX hydrolase is to sanitize the nucleotide pools and to maintain cell viability, thereby serving as surveillance and "house-cleaning" enzymes. Substrate specificity is used to define child families within the superfamily. Differences in substrate specificity are determined by the N-terminal extension or by residues in variable loop regions. Mechanistically, substrate hydrolysis occurs by a nucleophilic substitution reaction, with variation in the numbers and roles of divalent cations required. This superfamily consists of at least nine families: IPP (isopentenyl diphosphate) isomerase, ADP ribose pyrophosphatase, mutT pyrophosphohydrolase, coenzyme-A pyrophosphatase, MTH1-7,8-dihydro-8-oxoguanine-triphosphatase, diadenosine tetraphosphate hydrolase, NADH pyrophosphatase, GDP-mannose hydrolase and the c-terminal portion of the mutY adenine glycosylase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 964749142  19 GLLHRAFSVFLFNTEN-KLLLQQRSDAKITFPGCFTNTCCSHPLSNpaeleESdalgVRRAAQRRLKAELGIpleEVPPE 97
Cdd:cd04692   23 GLWHRTVHVWLVNPEEgRLLLQKRSANKDDFPGLWDISAAGHIDAG-----ET----YEEAAVRELEEELGL---TVSPE 90

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 964749142  98 EINYLTRIHYKAQSDGIWGeHEIDYILLVRKNVTLN---PDPNEI 139
Cdd:cd04692   91 DLIFLGVIREEVIGGDFID-NEFVHVYLYETDRPLEefkLQPEEV 134

uncharacterized NUDIX hydrolase subfamily; NUDIX hydrolase is a superfamily of enzymes found in all three kingdoms of life, and it catalyzes the hydrolysis of NUcleoside DIphosphates linked to other moieties, X. Enzymes belonging to this superfamily require a divalent cation, such as Mg2+ or Mn2+ for their activity. Members of this family are recognized by a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V), which forms a structural motif that functions as a metal binding and catalytic site. Substrates of NUDIX hydrolase include intact and oxidatively damaged nucleoside triphosphates, dinucleoside polyphosphates, nucleotide-sugars and dinucleotide enzymes. These substrates are metabolites or cell signaling molecules that require regulation during different stages of the cell cycle or during periods of stress. In general, the role of the NUDIX hydrolase is to sanitize the nucleotide pools and to maintain cell viability, thereby serving as surveillance and "house-cleaning" enzymes. Substrate specificity is used to define child families within the superfamily. Differences in substrate specificity are determined by the N-terminal extension or by residues in variable loop regions. Mechanistically, substrate hydrolysis occurs by a nucleophilic substitution reaction, with variation in the numbers and roles of divalent cations required. This superfamily consists of at least nine families: IPP (isopentenyl diphosphate) isomerase, ADP ribose pyrophosphatase, mutT pyrophosphohydrolase, coenzyme-A pyrophosphatase, MTH1-7,8-dihydro-8-oxoguanine-triphosphatase, diadenosine tetraphosphate hydrolase, NADH pyrophosphatase, GDP-mannose hydrolase and the c-terminal portion of the mutY adenine glycosylase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 964749142  16 LLHGLLHRAFSVFLFNTENKLLLQQRSDAKITFPGCFTNTCCSHPLSNpaelEESdalgvRRAAQRRLKAELGIpleEVP 95
Cdd:cd04693   23 LPEGEYHLVVHVWIFNSDGEILIQQRSPDKKGFPGMWEASTGGSVLAG----ETS-----LEAAIRELKEELGI---DLD 90

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 964749142  96 PEEINYLTRIHYkaqsdgiwgEHEIDYILLVRKNVTLN---PDPNEIKSYCYVS 146
Cdd:cd04693   91 ADELRPILTIRF---------DNGFDDIYLFRKDVDIEdltLQKEEVQDVKWVT 135

NUDIX domain family found in Deinococcus radiodurans, and similar proteins; Deinococcus radiodurans protein DR_0079 is one of 21 NUDIX hydrolases that it encodes, and it has been observed to have a marked preference for cytosine ribonucleoside 5'-diphosphate (CDP) and cytosine ribonucleoside 5'-triphosphate (CTP), and for their corresponding deoxyribose nucleotides, dCDP and dCTP, to a lesser degree. Members of the NUDIX hydrolase superfamily catalyze the hydrolysis of NUcleoside DIphosphates linked to other moieties, X. Enzymes belonging to this superfamily require a divalent cation, such as Mg2+ or Mn2+, for their activity and contain a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V), which functions as a metal binding and catalytic site. Substrates of NUDIX hydrolases include intact and oxidatively damaged nucleoside triphosphates, dinucleoside polyphosphates, nucleotide-sugars and dinucleotide enzymes. These substrates are metabolites or cell signaling molecules that require regulation during different stages of the cell cycle or during periods of stress. In general, the role of the NUDIX hydrolase is to sanitize the nucleotide pools and to maintain cell viability, thereby serving as surveillance _ "house-cleaning" enzymes. Substrate specificity is used to define families within the superfamily. Differences in substrate specificity are determined by the N-terminal extension or by residues in variable loop regions. Mechanistically, substrate hydrolysis occurs by a nucleophilic substitution reaction, with variation in the numbers and roles of divalent cations required.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 964749142  23 RAFSVFLFNTENKLLLQQRSDAKITFPGCFTNTCCSHPLSNpaelEESDAlgvrrAAQRRLKAELGIPLEEVPPEEINYL 102
Cdd:cd24154    3 RVVNAFLINSQGQLWIPRRTADKRIFPLALDMSVGGHVSSG----ETYEQ-----AFVRELQEELNLDLDQLSYRVLGKL 73

                 .
gi 964749142 103 T 103
Cdd:cd24154   74 T 74

NUDIX hydrolase superfamily; NUDIX hydrolase is a superfamily of enzymes found in all three kingdoms of life, and it catalyzes the hydrolysis of NUcleoside DIphosphates linked to other moieties, X. Enzymes belonging to this superfamily require a divalent cation, such as Mg2+ or Mn2+ for their activity. Members of this family are recognized by a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V), which forms a structural motif that functions as a metal binding and catalytic site. Substrates of NUDIX hydrolase include intact and oxidatively damaged nucleoside triphosphates, dinucleoside polyphosphates, nucleotide-sugars and dinucleotide enzymes. These substrates are metabolites or cell signaling molecules that require regulation during different stages of the cell cycle or during periods of stress. In general, the role of the NUDIX hydrolase is to sanitize the nucleotide pools and to maintain cell viability, thereby serving as surveillance and "house-cleaning" enzymes. Substrate specificity is used to define child families within the superfamily. Differences in substrate specificity are determined by the N-terminal extension or by residues in variable loop regions. Mechanistically, substrate hydrolysis occurs by a nucleophilic substitution reaction, with variation in the numbers and roles of divalent cations required. This superfamily consists of at least nine families: IPP (isopentenyl diphosphate) isomerase, ADP ribose pyrophosphatase, mutT pyrophosphohydrolase, coenzyme-A pyrophosphatase, MTH1-7,8-dihydro-8-oxoguanine-triphosphatase, diadenosine tetraphosphate hydrolase, NADH pyrophosphatase, GDP-mannose hydrolase and the c-terminal portion of the mutY adenine glycosylase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 964749142  26 SVFLFNTENKLLLQQRSDA----KITFPGCFtntccshplsnpAELEESdalgVRRAAQRRLKAELGIPLEEVPPEEINY 101
Cdd:cd02883    4 GAVVFDDEGRVLLVRRSDGpgpgGWELPGGG------------VEPGET----PEEAAVREVREETGLDVEVLRLLGVYE 67

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 964749142 102 LTRIHYKAQSDGIWgeheidYILLVRKNVTLNPDPNEIKSYCYVS 146
Cdd:cd02883   68 FPDPDEGRHVVVLV------FLARVVGGEPPPLDDEEISEVRWVP 106