GDP-mannose hydrolase (GDPMK), and similar proteins; GDP-mannose hydrolase (GDPMK) is a NUDIX enzyme that uses GDP-mannose as the preferred substrate. It is distinct from Nudix ADP-ribose hydrolases. GDPMK and ADP-ribose pyrophosphatase seem to use similar catalytic mechanism. However, GDPMK hydrolysis does not rely on a single glutamate as the catalytic base; rather, it is dependent on residues that coordinate the magnesium ions and residues that position the substrate properly for catalysis. 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 556299312  45 YDRGNGATILLYNREKKTVILTRQFRFPVFINGHEDDLIEAAAGLLDNMDPESRIKAEAEEETGFHVTRVEKIFEAYMSP 124
Cdd:cd24157    1 YDRGDAAAVLLYDPKRKTVVLVRQFRAPAYLGGGDGWLIEACAGLLDGDDPEDCIRREAEEETGYRLGDLEKVFTAYSSP 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 556299312 125 GSVTEKLYFYLAEYQPKDRTGAGGGIKAEGEDIDVLEMTLEEALRRIETGRIVDGKTIMLLYHIAL 190
Cdd:cd24157   81 GIVTERIHLFIAEYSSADRVGAGGGLAEEGEDIEVLELPLDEALAMIETGEIRDAKTIILLQYLRL 146

GDP-mannose hydrolase (GDPMK), and similar proteins; GDP-mannose hydrolase (GDPMK) is a NUDIX enzyme that uses GDP-mannose as the preferred substrate. It is distinct from Nudix ADP-ribose hydrolases. GDPMK and ADP-ribose pyrophosphatase seem to use similar catalytic mechanism. However, GDPMK hydrolysis does not rely on a single glutamate as the catalytic base; rather, it is dependent on residues that coordinate the magnesium ions and residues that position the substrate properly for catalysis. 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 556299312  45 YDRGNGATILLYNREKKTVILTRQFRFPVFINGHEDDLIEAAAGLLDNMDPESRIKAEAEEETGFHVTRVEKIFEAYMSP 124
Cdd:cd24157    1 YDRGDAAAVLLYDPKRKTVVLVRQFRAPAYLGGGDGWLIEACAGLLDGDDPEDCIRREAEEETGYRLGDLEKVFTAYSSP 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 556299312 125 GSVTEKLYFYLAEYQPKDRTGAGGGIKAEGEDIDVLEMTLEEALRRIETGRIVDGKTIMLLYHIAL 190
Cdd:cd24157   81 GIVTERIHLFIAEYSSADRVGAGGGLAEEGEDIEVLELPLDEALAMIETGEIRDAKTIILLQYLRL 146

nudix-type nucleoside diphosphatase, YffH/AdpP family; Members of this family include proteins of about 200 amino acids, including the recently characterized nudix hydrolase YffH, shows to be highly active as a GDP-mannose pyrophosphatase. It also includes the C-terminal half of a 361-amino acid protein, TrgB from Rhodobacter sphaeroides, shown experimentally to help confer tellurite resistance. This model also hits a region near the C-terminus of a 1092-amino acid protein of C. elegans. [Unknown function, Enzymes of unknown specificity]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 556299312    7 DVRIINSETLSDNWYILKKYTF-DLQRRDGEWQRQQREVYDRGNGATILLYNREKKTVILTRQFRFPVFINGHED-DLIE 84
Cdd:TIGR00052   2 QQEIIIKDTLYSGFFSLLHNIFyHRLFKGGESIRVTREIYDRGNAAAVLLYDPKKDTVVLIEQFRIAAYVNGEEPwLLEL 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 556299312   85 AAAGLLDNMDPESRIKAEAEEETGFHVTRVEKIFEAYMSPGSVTEKLYFYLAEYQPKDRTGAGGGikAEGEDIDVLEMTL 164
Cdd:TIGR00052  82 SAGMVEKGESPEDVARREAIEEAGYQVKNLRKLLSFYMSPGGVTELIHLFIAEVDDNQAAGIGGG--ADEEEIEVLHLVF 159

                         170       180
                  ....*....|....*....|.
gi 556299312  165 EEALRRIETGRIVDGKTIMLL 185
Cdd:TIGR00052 160 SQALQWIKEGKIDNGKTVILL 180

GDP-mannose hydrolase (GDPMK), and similar proteins; GDP-mannose hydrolase (GDPMK) is a NUDIX enzyme that uses GDP-mannose as the preferred substrate. It is distinct from Nudix ADP-ribose hydrolases. GDPMK and ADP-ribose pyrophosphatase seem to use similar catalytic mechanism. However, GDPMK hydrolysis does not rely on a single glutamate as the catalytic base; rather, it is dependent on residues that coordinate the magnesium ions and residues that position the substrate properly for catalysis. 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 556299312  45 YDRGNGATILLYNREKKTVILTRQFRFPVFINGHEDDLIEAAAGLLDNMDPESRIKAEAEEETGFHVTRVEKIFEAYMSP 124
Cdd:cd24157    1 YDRGDAAAVLLYDPKRKTVVLVRQFRAPAYLGGGDGWLIEACAGLLDGDDPEDCIRREAEEETGYRLGDLEKVFTAYSSP 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 556299312 125 GSVTEKLYFYLAEYQPKDRTGAGGGIKAEGEDIDVLEMTLEEALRRIETGRIVDGKTIMLLYHIAL 190
Cdd:cd24157   81 GIVTERIHLFIAEYSSADRVGAGGGLAEEGEDIEVLELPLDEALAMIETGEIRDAKTIILLQYLRL 146

nudix-type nucleoside diphosphatase, YffH/AdpP family; Members of this family include proteins of about 200 amino acids, including the recently characterized nudix hydrolase YffH, shows to be highly active as a GDP-mannose pyrophosphatase. It also includes the C-terminal half of a 361-amino acid protein, TrgB from Rhodobacter sphaeroides, shown experimentally to help confer tellurite resistance. This model also hits a region near the C-terminus of a 1092-amino acid protein of C. elegans. [Unknown function, Enzymes of unknown specificity]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 556299312    7 DVRIINSETLSDNWYILKKYTF-DLQRRDGEWQRQQREVYDRGNGATILLYNREKKTVILTRQFRFPVFINGHED-DLIE 84
Cdd:TIGR00052   2 QQEIIIKDTLYSGFFSLLHNIFyHRLFKGGESIRVTREIYDRGNAAAVLLYDPKKDTVVLIEQFRIAAYVNGEEPwLLEL 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 556299312   85 AAAGLLDNMDPESRIKAEAEEETGFHVTRVEKIFEAYMSPGSVTEKLYFYLAEYQPKDRTGAGGGikAEGEDIDVLEMTL 164
Cdd:TIGR00052  82 SAGMVEKGESPEDVARREAIEEAGYQVKNLRKLLSFYMSPGGVTELIHLFIAEVDDNQAAGIGGG--ADEEEIEVLHLVF 159

                         170       180
                  ....*....|....*....|.
gi 556299312  165 EEALRRIETGRIVDGKTIMLL 185
Cdd:TIGR00052 160 SQALQWIKEGKIDNGKTVILL 180

ADP-ribose pyrophosphatase, UDP-glucose pyrophosphatase, and similar proteins; ADP-ribose pyrophosphatase (ADPRase) ( NUDIX (Nucleoside diphosphate-linked moiety X)) motif 5; Nudt5) catalyzes the hydrolysis of ADP-ribose and a variety of additional ADP-sugar conjugates to AMP and ribose-5-phosphate. In humans, there are four distinct ADPRase activities, three putative cytosolic enzymes (ADPRase-I, -II, and -Mn) and a single mitochondrial enzyme (ADPRase-m). Human ADPRase-II is also referred to as NUDT5. It lacks the N-terminal target sequence unique to mitochondrial ADPRase. The different cytosolic types are distinguished by their specificities for substrate and specific requirement for metal ions. NUDT5 forms a homodimer. It also contains a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V) which functions as a metal binding site/catalytic site. In addition to the NUDIX motif, there are additional conserved amino acid residues, distal from the signature sequence, that correlate with substrate specificity. UDP-glucose pyrophosphatase (UGPPase) (EC 3.6.1.45; also known as nucleoside diphosphate-linked moiety X)) motif 14; Nudt14) hydrolyzes the pyrophosphate of the nucleoside diphosphate sugar to generate glucose-1-P and UMP. In mammals, UDP-glucose is the glucosyl donor for the synthesis of the storage polysaccharide glycogen. UGPPase, as a regulator of UDP-glucose, could play a regulatory role, but it has been shown to prefer ADP-ribose over UDP-glucose. Like other members of the NUDIX hydrolase superfamily, it requires a divalent cation, such as Mg2+, for its activity. It also contains a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V) which functions as a metal binding site/catalytic site.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 556299312  47 RGNGATILLYNREKKtVILTRQFRFPVfinghEDDLIEAAAGLLD-NMDPESRIKAEAEEETGFHVTRVEKIFEAYMSPG 125
Cdd:cd03424    1 HPGAVAVLAITDDGK-VVLVRQYRHPV-----GRVLLELPAGKIDpGEDPEEAARRELEEETGYTAGDLELLGSFYPSPG 74

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 556299312 126 SVTEKLYFYLAEYQPKDRTGAGGgikaEGEDIDVLEMTLEEALRRIETGRIVDGKTIMLLY 186
Cdd:cd03424   75 FSDERIHLFLAEDLTPVSEQALD----EDEFIEVVLVPLEEALEMIEDGEITDAKTLAALL 131

ADP-ribose pyrophosphatase NudF; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 556299312   5 RADVRIINSETLSDNWYILKKYTFDLQRRDGEWQRQ-QREVYDRGNGATILLYNREKKTVILTRQFRFPVFINGHEDDLI 83
Cdd:PRK10729   5 KNDVEIIARETLYRGFFSLDLYRFRHRLFNGEMSGEvRREIFERGHAAVLLPFDPVRDEVVLIEQIRIAAYDTSETPWLL 84

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 556299312  84 EAAAGLLD-NMDPESRIKAEAEEETGFHVTRVEKIFEAYMSPGSVTEKLYFYLAEYqpkDRTGAGG--GIKAEGEDIDVL 160
Cdd:PRK10729  85 EMVAGMIEeGESVEDVARREAIEEAGLIVGRTKPVLSYLASPGGTSERSSIMVGEV---DATTASGihGLADENEDIRVH 161

                        170       180       190
                 ....*....|....*....|....*....|
gi 556299312 161 EMTLEEALRRIETGRIVDGKTIMLLYHIAL 190
Cdd:PRK10729 162 VVSREQAYQWVEEGKIDNAASVIALQWLQL 191

NUDIX family Ndx2; NUDIX family protein Ndx2 found in Thermus thermophilus has ADP-ribose pyrophosphatase (ADPRase) as well as flavin adenine dinucleotide (FAD) activity. ADPRase (EC 3.6.1.13) catalyzes the hydrolysis of ADP-ribose to AMP and ribose-5-P. Like other members of the NUDIX hydrolase superfamily of enzymes, it is thought to require a divalent cation, such as Mg2+, for its activity. It also contains a 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V) which functions as a metal binding site/catalytic site. In addition to the NUDIX motif, there are additional conserved amino acid residues, distal from the signature sequence, that correlate with substrate specificity.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 556299312  62 TVILTRQFRFPV------FINGH---EDDLIEAAaglldnmdpesriKAEAEEETGFHVTRVEKIFEAYMSPGSVTEKLY 132
Cdd:cd24161   16 EVVLVEQYRYPLggwsweIPAGGwpeGEDPEEAA-------------RRELREETGLRAERWTPLGRFYPSNGVSDERAH 82

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 556299312 133 FYLAeyqpkdrTG--AGGGIKAEGE-DIDVLEMTLEEALRRIETGRIVDGKTIMLLYHIALK 191
Cdd:cd24161   83 VFLA-------TGltPGEPAPEETEeDLEVRRVPLAEALAMVLDGEITDAMSVAALLLARLH 137

ADP-ribose pyrophosphatase; ADP-ribose pyrophosphatase (ADPRase) (also known as NUDIX (Nucleoside diphosphate-linked moiety X)) motif 5; Nudt5) catalyzes the hydrolysis of ADP-ribose and a variety of additional ADP-sugar conjugates to AMP and ribose-5-phosphate. In humans, there are four distinct ADPRase activities, three putative cytosolic enzymes (ADPRase-I, -II, and -Mn) and a single mitochondrial enzyme (ADPRase-m). Human ADPRase-II is also referred to as NUDT5. It lacks the N-terminal target sequence unique to mitochondrial ADPRase. The different cytosolic types are distinguished by their specificities for substrate and specific requirement for metal ions. NUDT5 forms a homodimer. It also contains a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V) which functions as a metal binding site/catalytic site. In addition to the NUDIX motif, there are additional conserved amino acid residues, distal from the signature sequence, that correlate with substrate specificity.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 556299312  52 TILLYNREKKTVILTRQFRFPVfiNGHeddLIEAAAGLLD-NMDPESRIKAEAEEETGFHVTRVEKIFEA-YMSPGSVTE 129
Cdd:cd18888    9 AILKRKLKPPELVLVKQYRPPV--NAY---TIEFPAGLVDpGESPEQAALRELKEETGYTGEKVLSVSPPlALDPGLSNA 83

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 556299312 130 KLYFYLAEYQ--------PKDRTGagggikaEGEDIDVLEMTLEEALRRI-----ETGRIVDGKtimlLYHIAL 190
Cdd:cd18888   84 NMKLVTVEVDgddpenqnPKQELE-------DGEFIEVILVPLNELLERLqelakEEGYAIDAR----LYSFAL 146

ADP-ribose pyrophosphatase from Mycobacterium tuberculosis (Mt-ADPRase), and similar proteins; Mycobacterium tuberculosis ADP-ribose pyrophosphatase mt-ADPRase(also called Rv1700) is a NUDIX protein that catalyzes the hydrolysis of ADP-ribose and a variety of additional ADP-sugar conjugates to AMP and ribose-5-phosphate. In humans, there are four distinct ADPRase activities, three putative cytosolic enzymes (ADPRase-I, -II, and -Mn) and a single mitochondrial enzyme (ADPRase-m). Human ADPRase-II is also referred to as NUDT5. It lacks the N-terminal target sequence unique to mitochondrial ADPRase. The different cytosolic types are distinguished by their specificities for substrate and specific requirement for metal ions. NUDT5 forms a homodimer. It also contains a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V) which functions as a metal binding site/catalytic site. In addition to the NUDIX motif, there are additional conserved amino acid residues, distal from the signature sequence, that correlate with substrate specificity. UDP-glucose pyrophosphatase (UGPPase) (EC 3.6.1.45; also known as nucleoside diphosphate-linked moiety X)) motif 14; Nudt14) hydrolyzes the pyrophosphate of the nucleoside diphosphate sugar to generate glucose-1-P and UMP. In mammals, UDP-glucose is the glucosyl donor for the synthesis of the storage polysaccharide glycogen. UGPPase, as a regulator of UDP-glucose, could play a regulatory role, but it has been shown to prefer ADP-ribose over UDP-glucose. Like other members of the NUDIX hydrolase superfamily, it requires a divalent cation, such as Mg2+, for its activity. It also contains a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V) which functions as a metal binding site/catalytic site.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 556299312   9 RIINSETLSDNWYI-LKKYTFDLqrrdGEWQRQQREVYDRGnGATILLYNREKKTVILTRQFRFPVfinGHEddLIEAAA 87
Cdd:cd24158    1 PVLSSEVVYEGAIWdVRRDTVDL----PGGGTVTREYVEHP-GAVAVVALDDDGRVLLIRQYRHPV---RRR--LWELPA 70

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 556299312  88 GLLDnMDPESRIKA---EAEEETGFHVTRVEKIFEAYMSPGSVTEKLYFYLA----EYQPKDRTGAgggiKAEGEDIDVL 160
Cdd:cd24158   71 GLLD-VAGEPPLEAaarELAEEADLEAARWEVLVDLFTSPGFSSEAVRVYLArglsEVPEADRHER----EDEEADMTLR 145

                        170       180
                 ....*....|....*....|...
gi 556299312 161 EMTLEEALRRIETGRIVDGKTIM 183
Cdd:cd24158  146 WVPLDEAVAAVLAGRITNSTAVA 168