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 735018273  20 VANVVVYRDVDKkCLLLKRSENEkvHPGKYCVPGGKLEWNDlpldmptringdvlDYQDTieklLLREVKEETGLLIHN- 98
Cdd:cd02883    2 AVGAVVFDDEGR-VLLVRRSDGP--GPGGWELPGGGVEPGE--------------TPEEA----AVREVREETGLDVEVl 60

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 735018273  99 KLCYINSVGFiRPDGIPVVLTKFAARYKAGD-VVLEKGSFTDHAWVD 144
Cdd:cd02883   61 RLLGVYEFPD-PDEGRHVVVLVFLARVVGGEpPPLDDEEISEVRWVP 106

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 735018273  20 VANVVVYRDVDKkCLLLKRSENEkvHPGKYCVPGGKLEWNDlpldmptringdvlDYQDTieklLLREVKEETGLLIHN- 98
Cdd:cd02883    2 AVGAVVFDDEGR-VLLVRRSDGP--GPGGWELPGGGVEPGE--------------TPEEA----AVREVREETGLDVEVl 60

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 735018273  99 KLCYINSVGFiRPDGIPVVLTKFAARYKAGD-VVLEKGSFTDHAWVD 144
Cdd:cd02883   61 RLLGVYEFPD-PDEGRHVVVLVFLARVVGGEpPPLDDEEISEVRWVP 106

NUDIX domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 735018273   20 VANVVVYRDvDKKCLLLKRSEneKVHPGKYCVPGGKLEWNDlpldmptringdvldyqdTIEKLLLREVKEETGLLIHN- 98
Cdd:pfam00293   5 AVGVVLLNE-KGRVLLVRRSK--KPFPGWWSLPGGKVEPGE------------------TPEEAARRELEEETGLEPELl 63

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 735018273   99 ----KLCYINSVGFIRPDGiPVVLTKFAARYKAGDVVLEKGSFTDHAWVD 144
Cdd:pfam00293  64 ellgSLHYLAPFDGRFPDE-HEILYVFLAEVEGELEPDPDGEVEEVRWVP 112

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 735018273  20 VANVVVYRDVDKkCLLLKRSENEkvHPGKYCVPGGKLEWNDlpldmptringdvlDYQDTieklLLREVKEETGLLIHN- 98
Cdd:cd02883    2 AVGAVVFDDEGR-VLLVRRSDGP--GPGGWELPGGGVEPGE--------------TPEEA----AVREVREETGLDVEVl 60

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 735018273  99 KLCYINSVGFiRPDGIPVVLTKFAARYKAGD-VVLEKGSFTDHAWVD 144
Cdd:cd02883   61 RLLGVYEFPD-PDEGRHVVVLVFLARVVGGEpPPLDDEEISEVRWVP 106

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 735018273  20 VANVVVYRDvDKKCLLLKRSENeKVHPGKYCVPGGKLEWNDLPLDmptringdvldyqdtiekLLLREVKEETGLLIHNk 99
Cdd:COG0494   15 AVVVVLLDD-DGRVLLVRRYRY-GVGPGLWEFPGGKIEPGESPEE------------------AALRELREETGLTAED- 73

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 735018273 100 lcyINSVG-FIRPDGIPVVLTKFAARY--KAGDVVL-EKGSFTDHAWVDDSDVGEYdciqGIAQEIQEAIAMFK 169
Cdd:COG0494   74 ---LELLGeLPSPGYTDEKVHVFLARGlgPGEEVGLdDEDEFIEVRWVPLDEALAL----VTAGEIAKTLAALA 140

MutT homolog-1 and similar proteins; MutT homolog-1 (MTH1), also known as NUDIX (nucleoside diphosphate-linked moiety X)) motif 1/Nudt1, is a member of the NUDIX hydrolase superfamily. MTH1, the mammalian counterpart of MutT, hydrolyzes oxidized purine nucleoside triphosphates, such as 8-oxo-dGTP and 2-hydroxy-ATP, to monophosphates, thereby preventing the incorporation of such oxygen radicals during replication. This is an important step in the repair mechanism in genomic and mitochondrial DNA. Like other members of the NUDIX family, it requires a divalent cation, such as Mg2+ or Mn2+, for activity, and contain 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. MTH1 is predominantly localized in the cytoplasm and mitochondria. Structurally, this enzyme adopts a similar fold to MutT despite low sequence similarity outside the conserved NUDIX motif. The most distinctive structural difference between MutT and MTH1 is the presence of a beta-hairpin, which is absent in MutT. This results in a much deeper and narrower substrate binding pocket. Mechanistically, MTH1 contains dual specificity for nucleotides that contain 2-OH-adenine bases and those that contain 8-oxo-guanine bases.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 735018273  17 FYFVANVVVYRDvdKKCLLLKRSENEkvhPGKYCVPGGKLEwndlpldmptringdvldYQDTIEKLLLREVKEETGLLI 96
Cdd:cd04699    1 FPVSVKGVIFDN--GRVLLLRRSRAG---AGEWELPGGRLE------------------PGESPEEALKREVKEETGLDV 57

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 735018273  97 H-NKLCYinSVGFIRPDGIPVVLTKFAARYKAGDVVLekgSF--TDHAWVDDSDVGEYDCIQG 156
Cdd:cd04699   58 SvGELLD--TWTFELDPDKGVFIVTYLCRLVGGEVTL---SDehEEYEWVTPEELAELELPEG 115

Nucleoside diphosphate-linked moiety X)) motif 19; Acyl CoA diphosphohydrolase (also known as NUDIX (nucleoside diphosphate linked moiety X))-type motif 10; Nudt19; testosterone-regulated protein rp2) has activity towards CoA, oxidized CoA and a wide range of CoA esters, including choloyl-CoA and branched-chain fatty-acyl-CoA esters. CoA is the major acyl carrier in mammals and a key cofactor in energy metabolism. Dynamic regulation of CoA in different tissues and organs supports metabolic flexibility. 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 735018273  21 ANVVVYRDVDK--KCLLLKRSENEKVHPGKYCVPGGKLEWNDLPLDMPTRINGDVLDYQDTIEKLL---------LREVK 89
Cdd:cd18870    3 ATVILLRDGADglEVLLLRRSSTMSFMPGAYVFPGGRVDPADRDAPWAGLLPPDVASASRPGKSDPearalriaaIRETF 82

                 ....*..
gi 735018273  90 EETGLLI 96
Cdd:cd18870   83 EETGLLL 89

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 735018273  47 GKYCVPGGKLEWNDlpldmptringdvldyqdTIEKLLLREVKEETGLLIHN-KLCY----INSVGFIRPDGIpvVLTKF 121
Cdd:cd18874   26 DLYGIPGGKVEWGE------------------TLEEALKREVKEETGLDITDiRFILvqesINSEEFHKPAHF--VFVDY 85

                         90       100       110
                 ....*....|....*....|....*....|.
gi 735018273 122 AARYKAGDVVLEKgSFTDHAWVDDSDVGEYD 152
Cdd:cd18874   86 LARTDSSEVVLNE-EAVEYLWVEPEEALKYP 115

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        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 735018273  20 VANVVVYRDVDKKCLLLKRSENEKVHPGKYCVPGGKLEWNdlpldmptringdvldyqDTIEKLLLREVKEETGL 94
Cdd:cd04694    3 VGVVVLIEDSDDRVLLTRRAKHMRTFPGVWVPPGGHVELG------------------ESLLEAGLRELQEETGL 59

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 735018273  34 LLLKRSENEKVHPGKYCVPGGKLEWNDlpldmptringdvLDYQDTieklLLREVKEETGLLIHN 98
Cdd:cd03426   19 LLTKRASHLRSHPGQIAFPGGKREPGD-------------ESPVET----ALRETEEEIGLPPES 66

MutT pyrophosphohydrolase; The MutT pyrophosphohydrolase is a prototypical NUDIX hydrolase that catalyzes the hydrolysis of nucleoside and deoxynucleoside triphosphates (NTPs and dNTPs) by substitution at a beta-phosphorus to yield a nucleotide monophosphate (NMP) and inorganic pyrophosphate (PPi). This enzyme requires two divalent cations for activity; one coordinates the phosphoryl groups of the NTP/dNTP substrate, and the other coordinates to the enzyme. It also contains the NUDIX motif, a highly conserved 23-residue block (GX5EX7REUXEEXGU, where U = I, L or V), that functions as metal binding and catalytic site. MutT pyrophosphohydrolase is important in preventing errors in DNA replication by hydrolyzing mutagenic nucleotides such as 8-oxo-dGTP (a product of oxidative damage), which can mispair with template adenine during DNA replication, to guanine nucleotides.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 735018273  30 DKKCLLLKRSENeKVHPGKYCVPGGKLEWNdlpldmptringdvldyqDTIEKLLLREVKEETGLLIHNkLCYINSVGFI 109
Cdd:cd03425   11 DGRVLIAQRPEG-KHLAGLWEFPGGKVEPG------------------ETPEQALVRELREELGIEVEV-GEPLGTVEHD 70

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 735018273 110 RPDGIpVVLTKFAARYKAGDVVLEKGSftDHAWVDDSDVGEYD 152
Cdd:cd03425   71 YPDFH-VRLHVYLCTLWSGEPQLLEHQ--ELRWVTPEELDDLD 110

NUDIX hydrolase subfamily; Nucleoside triphosphatase NudI catalyzes the hydrolysis of nucleoside triphosphates, with a preference for pyrimidine deoxynucleoside triphosphates (dUTP, dTTP and dCTP). It is a members of the NUDIX hydrolase superfamily which 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 735018273  34 LLLKRSENEKVHPGKYCVPGGKLEWNDlpldmptringdvldyqdTIEKLLLREVKEETGLLIhnKLCYINSVGF---IR 110
Cdd:cd04696   16 LLCKMADDRGVFPGQWALSGGGVEPGE------------------RIEEALRREIREELGEQL--ILSDITPWTFrddIR 75

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 735018273 111 ----PDG----IPVVLTKFAARYKAGDVVLEKgSFTDHAWVDDSDVGEYD 152
Cdd:cd04696   76 iktyPDGrqeeIYMIYLIFDCVSANRDVCIND-EFQDYAWVKPADLANYD 124

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 735018273  14 NKLFYFVANVVVyRDVDKKCLLLKRSENEKVHPGKY-CVPGGKlewndlpldmptringdVLDYQDTIEKLLlREVKEET 92
Cdd:cd04693   25 EGEYHLVVHVWI-FNSDGEILIQQRSPDKKGFPGMWeASTGGS-----------------VLAGETSLEAAI-RELKEEL 85

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 735018273  93 GLLIHN-KLCYINSV----GFirpDGIPVVLTKFaaryKAGDVVLEKGSFTDHAWVDDSDV 148
Cdd:cd04693   86 GIDLDAdELRPILTIrfdnGF---DDIYLFRKDV----DIEDLTLQKEEVQDVKWVTLEEI 139

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 735018273  19 FVANVVVYRDVDKkCLLLKRSENEKV-HPGKYCVPGGKLEWNDLPLDMptringdvldyqdtieklLLREVKEETGLLI 96
Cdd:cd18882    2 EVAIAILYDDRGK-VLLQLRDDKPGIpYPGYWGLFGGHLEPGETPEEA------------------IRRELEEEIGYEP 61