coenzyme A pyrophosphatase and similar proteins; Coenzyme A pyrophosphatase (CoAse; EC 3.6.1.1), also called nucleoside diphosphate-linked moiety X)) motif 7, is a member of the NUDIX hydrolase superfamily, functions to catalyze the elimination of oxidized inactive CoA, which can inhibit CoA-utilizing enzymes. The need of CoAses mainly arises under conditions of oxidative stress. CoAse has a conserved NUDIX fold and requires a single divalent cation for catalysis. In addition to a signature NUDIX motif G[X5]E[X7]REUXEEXGU, where U is Ile, Leu, or Val, CoAse contains an additional motif upstream called the NuCoA motif (LLTXT(SA)X3RX3GX3FPGG) which is postulated to be involved in CoA recognition. CoA plays a central role in lipid metabolism. It is involved in the initial steps of fatty acid sythesis in the cytosol, in the oxidation of fatty acids and the citric acid cycle in the mitochondria, and in the oxidation of long-chain fatty acids in peroxisomes. CoA has the important role of activating fatty acids for further modification into key biological signalling molecules.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13384950  32 AAVLVPLCLVRGVPALLYTLRSSRLvGRHKGEVSFPGGKCDPDDQDVIHTALRETQEELGLEVPKEHVWGVLQPVYDREK 111
Cdd:cd03426   3 AAVLIPLVEGDGELHVLLTKRASHL-RSHPGQIAFPGGKREPGDESPVETALRETEEEIGLPPESVEVLGRLDPLYTPSG 81

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 13384950 112 ATIVPVLANVGPLDLqsLRPNLEEVDEVFEMSLAHLLQTQNQGYTHFCQGGHF-SYTLPVFLHGPHRVWGLTAVIT 186
Cdd:cd03426  82 FVVTPFVGLLDDPPP--LRPNPDEVAEVFTVPLSFLLDPEPRRYETFLRSGPRgTYRVPFYPYEGYVIWGLTARIL 155

coenzyme A pyrophosphatase and similar proteins; Coenzyme A pyrophosphatase (CoAse; EC 3.6.1.1), also called nucleoside diphosphate-linked moiety X)) motif 7, is a member of the NUDIX hydrolase superfamily, functions to catalyze the elimination of oxidized inactive CoA, which can inhibit CoA-utilizing enzymes. The need of CoAses mainly arises under conditions of oxidative stress. CoAse has a conserved NUDIX fold and requires a single divalent cation for catalysis. In addition to a signature NUDIX motif G[X5]E[X7]REUXEEXGU, where U is Ile, Leu, or Val, CoAse contains an additional motif upstream called the NuCoA motif (LLTXT(SA)X3RX3GX3FPGG) which is postulated to be involved in CoA recognition. CoA plays a central role in lipid metabolism. It is involved in the initial steps of fatty acid sythesis in the cytosol, in the oxidation of fatty acids and the citric acid cycle in the mitochondria, and in the oxidation of long-chain fatty acids in peroxisomes. CoA has the important role of activating fatty acids for further modification into key biological signalling molecules.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13384950  32 AAVLVPLCLVRGVPALLYTLRSSRLvGRHKGEVSFPGGKCDPDDQDVIHTALRETQEELGLEVPKEHVWGVLQPVYDREK 111
Cdd:cd03426   3 AAVLIPLVEGDGELHVLLTKRASHL-RSHPGQIAFPGGKREPGDESPVETALRETEEEIGLPPESVEVLGRLDPLYTPSG 81

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 13384950 112 ATIVPVLANVGPLDLqsLRPNLEEVDEVFEMSLAHLLQTQNQGYTHFCQGGHF-SYTLPVFLHGPHRVWGLTAVIT 186
Cdd:cd03426  82 FVVTPFVGLLDDPPP--LRPNPDEVAEVFTVPLSFLLDPEPRRYETFLRSGPRgTYRVPFYPYEGYVIWGLTARIL 155

8-oxo-dGTP pyrophosphatase MutT and related house-cleaning NTP pyrophosphohydrolases, NUDIX family [Defense mechanisms];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13384950  26 RSRPAAAAVLVP----LCLVRgvpallytlRSSRlvGRHKGEVSFPGGKCDPDDqDVIHTALRETQEELGLEVPKEHVWG 101
Cdd:COG0494  11 HYRPAVVVVLLDddgrVLLVR---------RYRY--GVGPGLWEFPGGKIEPGE-SPEEAALRELREETGLTAEDLELLG 78

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*....
gi 13384950 102 VLQ-PVYDREKATIVpVLANVGPLDLQSLRPNlEEVDEVFEMSLAHLLQ 149
Cdd:COG0494  79 ELPsPGYTDEKVHVF-LARGLGPGEEVGLDDE-DEFIEVRWVPLDEALA 125

coenzyme A pyrophosphatase and similar proteins; Coenzyme A pyrophosphatase (CoAse; EC 3.6.1.1), also called nucleoside diphosphate-linked moiety X)) motif 7, is a member of the NUDIX hydrolase superfamily, functions to catalyze the elimination of oxidized inactive CoA, which can inhibit CoA-utilizing enzymes. The need of CoAses mainly arises under conditions of oxidative stress. CoAse has a conserved NUDIX fold and requires a single divalent cation for catalysis. In addition to a signature NUDIX motif G[X5]E[X7]REUXEEXGU, where U is Ile, Leu, or Val, CoAse contains an additional motif upstream called the NuCoA motif (LLTXT(SA)X3RX3GX3FPGG) which is postulated to be involved in CoA recognition. CoA plays a central role in lipid metabolism. It is involved in the initial steps of fatty acid sythesis in the cytosol, in the oxidation of fatty acids and the citric acid cycle in the mitochondria, and in the oxidation of long-chain fatty acids in peroxisomes. CoA has the important role of activating fatty acids for further modification into key biological signalling molecules.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13384950  32 AAVLVPLCLVRGVPALLYTLRSSRLvGRHKGEVSFPGGKCDPDDQDVIHTALRETQEELGLEVPKEHVWGVLQPVYDREK 111
Cdd:cd03426   3 AAVLIPLVEGDGELHVLLTKRASHL-RSHPGQIAFPGGKREPGDESPVETALRETEEEIGLPPESVEVLGRLDPLYTPSG 81

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 13384950 112 ATIVPVLANVGPLDLqsLRPNLEEVDEVFEMSLAHLLQTQNQGYTHFCQGGHF-SYTLPVFLHGPHRVWGLTAVIT 186
Cdd:cd03426  82 FVVTPFVGLLDDPPP--LRPNPDEVAEVFTVPLSFLLDPEPRRYETFLRSGPRgTYRVPFYPYEGYVIWGLTARIL 155

nudix hydrolase

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13384950   20 RTTARLRSRPAAAAVLVplCLV------RGVPALLYTLRSSRLvGRHKGEVSFPGGKCDPDDQDVIHTALRETQEELGLE 93
Cdd:PLN02709  22 ETHLRQHFPAKSSAVLV--CLYqeqredKNELRVILTKRSSTL-SSHPGEVALPGGKRDEEDKDDIATALREAREEIGLD 98

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 13384950   94 VPKEHVWGVLQPVYDREKATIVPVLANVgpLDLQSLR--PNLEEVDEVFEMSLAHLLQTQNQ 153
Cdd:PLN02709  99 PSLVTIISVLEPFVNKKGMSVAPVIGFL--HDKKAFKplPNPAEVEEIFDVPLEMFLKDKNK 158

ADP-ribose pyrophosphatase YjhB, NUDIX family [Nucleotide transport and metabolism];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13384950  55 RLVGRHKGEVSFPGGKCDPDDqDVIHTALRETQEELGLEVPKEHVWGVLQpVYDREKATIVPVLANVGPLDLQslrpNLE 134
Cdd:COG1051  25 RADEPGKGLWALPGGKVEPGE-TPEEAALRELREETGLEVEVLELLGVFD-HPDRGHVVSVAFLAEVLSGEPR----ADD 98

                        90
                ....*....|....*
gi 13384950 135 EVDEVFEMSLAHLLQ 149
Cdd:COG1051  99 EIDEARWFPLDELPE 113

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 13384950  77 DVIHTALRETQEELGLEVPKEHVW--GVLQPVYDREKAT---IVPVLANVGPLDLQSLRPNLEEVDEVFEMSL 144
Cdd:cd04692  70 TYEEAAVRELEEELGLTVSPEDLIflGVIREEVIGGDFIdneFVHVYLYETDRPLEEFKLQPEEVAGVVFVDL 142

nucleoside diphosphate-linked moiety X)) motif 17; Nucleoside diphosphate-linked moiety X)) motif 17 (EC 3.6.1.-) encoded by the NUDT17 gene on chromosome 1q21.1 and encodes an enzyme thought to hydrolyse some nucleoside diphosphate derivatives. 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
                ....*....|....*....|....*....|....*...
gi 13384950  66 FPGGKCDPDdQDVIHTALRETQEELGLEVPKEHVWGVL 103
Cdd:cd04694  34 PPGGHVELG-ESLLEAGLRELQEETGLEVSDIQSLSLL 70

MutT homolog 2; MutT Homolog 2 (MTH2; EC 3.6.1.9), also known as NUDIX (nucleoside diphosphate-linked moiety X)) motif 15/Nudt15, may catalyze the hydrolysis of nucleoside diphosphates, triphosphates including dGTP, dTTP, dCTP, their oxidized forms like 8-oxo-dGTP, and prodrug thiopurine derivatives 6-thio-dGTP and 6-thio-GTP. MTH2 may also play a role in DNA synthesis and cell cycle progression by stabilizing PCNA. 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 13384950  56 LVGRHK-----GEVSFPGGKCDPDdQDVIHTALRETQEELGLEVPKEHVWGVLQPVYDREKATIVpVLANVGPLDLQSLR 130
Cdd:cd04678  17 LLGRRKgshgaGTWALPGGHLEFG-ESFEECAAREVLEETGLEIRNVRFLTVTNDVFEEEGKHYV-TIFVLAEVDDGEPE 94

                ....
gi 13384950 131 PNLE 134
Cdd:cd04678  95 ENME 98

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 13384950  66 FPGGKCDPDDqDVIHTALRETQEELGLEVPKEHVWGVLQ--PVYDREKATIvpVLA-NVGPLDLQSLRPNleEVDEVFEM 142
Cdd:cd03424  33 LPAGKIDPGE-DPEEAARRELEEETGYTAGDLELLGSFYpsPGFSDERIHL--FLAeDLTPVSEQALDED--EFIEVVLV 107

                        90
                ....*....|..
gi 13384950 143 SLAHLLQTQNQG 154
Cdd:cd03424 108 PLEEALEMIEDG 119

diadenosine hexaphosphate (Ap6A) hydrolase; Diadenosine hexaphosphate (Ap6A) hydrolase is a member of the NUDIX hydrolase superfamily. Ap6A hydrolase specifically hydrolyzes diadenosine polyphosphates, but not ATP or diadenosine triphosphate, and it generates ATP as the product. Ap6A, the most preferred substrate, hydrolyzes to produce two ATP molecules, which is a novel hydrolysis mode for Ap6A. These results indicate that Ap6A hydrolase is a diadenosine polyphosphate hydrolase. It requires the presence of a divalent cation, such as Mn2+, Mg2+, Zn2+, and Co2+, for activity. Members of the NUDIX hydrolase superfamily 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.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|
gi 13384950  56 LVGRHKG-EVSFPGGKCDPDdQDVIHTALRETQEELGLEV 94
Cdd:cd03673  20 LIHRPRYdDWSLPKGKLEPG-ETPEEAAVREVEEETGLRV 58

Predicted NTP pyrophosphohydrolase, NUDIX family [Nucleotide transport and metabolism, General function prediction only];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13384950  47 LLYTLRSSRL------------VGRHKGEVSFPGGKCDPDDqDVIHTALRETQEELGLEVPkEHVWGVLQPVydREKA-T 113
Cdd:COG4119   9 LLYRRRDGGLevllvhpggpfwARKDEGAWSIPKGEYEPGE-DPLAAARREFAEETGVPAP-DGPFIPLGEV--RQKSgK 84

                        90       100
                ....*....|....*....|....*....
gi 13384950 114 IVPVLANVGPLDLQSLRPNLeevdevFEM 142
Cdd:COG4119  85 VVTAWAVEGDLDPAAIVSNT------FEL 107

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
                ....*....|....*....|....*...
gi 13384950  67 PGGKCDPDDqDVIHTALRETQEELGLEV 94
Cdd:cd03674  30 PGGHVEPDE-DPLEAALREAREETGLDV 56

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
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 13384950  66 FPGGKCDPDdQDVIHTALRETQEELGLEVPKEHVwgVLQPVYDREKATIVPVLANVGPL 124
Cdd:cd04682  32 LPGGGREGD-ETPFACVLRELREELGLALPEDRL--VWERVYPSNHNPGRQSWFFVARL 87

adenosine nucleotide hydrolase NudE; Provisional

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 13384950   20 RTTARLRSRPAAAAVLVP------LCLVRGvpallYTlrssrlVGRHKGEVSFPGGKCDPdDQDVIHTALRETQEELGL 92
Cdd:PRK11762  37 RVYERMRPSGRGAVMIVPildddtLLLIRE-----YA------AGTERYELGFPKGLIDP-GETPLEAANRELKEEVGF 103

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
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 13384950  41 VRGVpALLYTLRSSRLVGRHKGE---VSFPGGKCDPDDQDvIHTALRETQEELGLEVPKE 97
Cdd:cd04669   1 VRAV-LVIYDDDKLLLIRRTKPGeeyYVFPGGGIEPGETP-EEAALREAVEELGLDVAVT 58