Adp Ribose Pyrophosphatase; ADP-ribose pyrophosphatase (ADPRase) 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 654549455  15 DVEIIAREMLYSGFFSMELYRFRHRLFNGEMSGEIRREIFERGHAAVLLPFDPVRDEVVLVEQIRIAAYDVSESPWLLEM 94
Cdd:cd24155    1 DVEILSKETVYDGFFRLERYRLRHRRFDGGWSAPLTREIFERGDAVAVLPYDPVRDEVVLIEQFRIGALARDESPWLLEI 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 654549455  95 VAGMIEEGESVEDVARREALEEAGLVVGRTKPVLSYLASPGGTSERLSIMVGEVDATTAEGIHGLADENEDIRVHVVSRE 174
Cdd:cd24155   81 VAGMIDAGETPEDVARREAEEEAGLTLDALEPIASYYPSPGGSTERVHLYLGLVDLSDLGGIHGLAEEGEDIRVHVVPFD 160

                        170       180
                 ....*....|....*....|....*..
gi 654549455 175 QAYQWVEEGKIDNAASVIALQWLQLHY 201
Cdd:cd24155  161 EAMALLDDGEIDNAPLIIALQWLALNR 187

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 654549455  45 MSGEIRREIFERGHAAVLLPFDPvRDEVVLVEQIRIAAYdvsesPWLLEMVAGMIEEGESVEDVARREALEEAGLVVGRT 124
Cdd:COG0494    1 MTEILSSEPEHYRPAVVVVLLDD-DGRVLLVRRYRYGVG-----PGLWEFPGGKIEPGESPEEAALRELREETGLTAEDL 74

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 654549455 125 KPVLSYLaSPGGTSERLSIMVGEVdaTTAEGIHGLADENEDIRVHVVSREQAYQWVEEGKIdnAASVIALQWLQ 198
Cdd:COG0494   75 ELLGELP-SPGYTDEKVHVFLARG--LGPGEEVGLDDEDEFIEVRWVPLDEALALVTAGEI--AKTLAALARLL 143

Adp Ribose Pyrophosphatase; ADP-ribose pyrophosphatase (ADPRase) 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 654549455  15 DVEIIAREMLYSGFFSMELYRFRHRLFNGEMSGEIRREIFERGHAAVLLPFDPVRDEVVLVEQIRIAAYDVSESPWLLEM 94
Cdd:cd24155    1 DVEILSKETVYDGFFRLERYRLRHRRFDGGWSAPLTREIFERGDAVAVLPYDPVRDEVVLIEQFRIGALARDESPWLLEI 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 654549455  95 VAGMIEEGESVEDVARREALEEAGLVVGRTKPVLSYLASPGGTSERLSIMVGEVDATTAEGIHGLADENEDIRVHVVSRE 174
Cdd:cd24155   81 VAGMIDAGETPEDVARREAEEEAGLTLDALEPIASYYPSPGGSTERVHLYLGLVDLSDLGGIHGLAEEGEDIRVHVVPFD 160

                        170       180
                 ....*....|....*....|....*..
gi 654549455 175 QAYQWVEEGKIDNAASVIALQWLQLHY 201
Cdd:cd24155  161 EAMALLDDGEIDNAPLIIALQWLALNR 187

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 654549455  54 FERGHAAVLLPFDPVRDEVVLVEQIRIAAYDVSESPWLLEMVAGMIeEGESVEDVARREALEEAGLVVGRTKPVLSYLAS 133
Cdd:cd24157    1 YDRGDAAAVLLYDPKRKTVVLVRQFRAPAYLGGGDGWLIEACAGLL-DGDDPEDCIRREAEEETGYRLGDLEKVFTAYSS 79

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 654549455 134 PGGTSERLSIMVGEVDAT--TAEGiHGLADENEDIRVHVVSREQAYQWVEEGKIDNAASVIALQWLQL 199
Cdd:cd24157   80 PGIVTERIHLFIAEYSSAdrVGAG-GGLAEEGEDIEVLELPLDEALAMIETGEIRDAKTIILLQYLRL 146

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 654549455  45 MSGEIRREIFERGHAAVLLPFDPvRDEVVLVEQIRIAAYdvsesPWLLEMVAGMIEEGESVEDVARREALEEAGLVVGRT 124
Cdd:COG0494    1 MTEILSSEPEHYRPAVVVVLLDD-DGRVLLVRRYRYGVG-----PGLWEFPGGKIEPGESPEEAALRELREETGLTAEDL 74

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 654549455 125 KPVLSYLaSPGGTSERLSIMVGEVdaTTAEGIHGLADENEDIRVHVVSREQAYQWVEEGKIdnAASVIALQWLQ 198
Cdd:COG0494   75 ELLGELP-SPGYTDEKVHVFLARG--LGPGEEVGLDDEDEFIEVRWVPLDEALALVTAGEI--AKTLAALARLL 143

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 654549455  17 EIIAREMLYSG-FFSMelyrfRHRLFNGEMSGEIRREIFERGHAAVLLPFDPvRDEVVLVEQIRIAaydVSESPWllEMV 95
Cdd:cd24158    1 PVLSSEVVYEGaIWDV-----RRDTVDLPGGGTVTREYVEHPGAVAVVALDD-DGRVLLIRQYRHP---VRRRLW--ELP 69

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 654549455  96 AGMIE-EGESVEDVARREALEEAGLVVGRTKPVLSYLASPGGTSERLSIMVGE-VDATTAEGIHGLADENEDIRVHVVSR 173
Cdd:cd24158   70 AGLLDvAGEPPLEAAARELAEEADLEAARWEVLVDLFTSPGFSSEAVRVYLARgLSEVPEADRHEREDEEADMTLRWVPL 149

                        170       180
                 ....*....|....*....|.
gi 654549455 174 EQAYQWVEEGKIDNAASVIAL 194
Cdd:cd24158  150 DEAVAAVLAGRITNSTAVAGV 170

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 654549455  70 DEVVLVEQIR--IAAYdvsespwLLEMVAGMIEEGESVEDVARREALEEAGLV---VGRTKPVLSYlaSPGGTSERLSIM 144
Cdd:cd18888   18 PELVLVKQYRppVNAY-------TIEFPAGLVDPGESPEQAALRELKEETGYTgekVLSVSPPLAL--DPGLSNANMKLV 88

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 654549455 145 VGEVDATTAEGIHGLA--DENEDIRVHVVSREQAYQWVEE 182
Cdd:cd18888   89 TVEVDGDDPENQNPKQelEDGEFIEVILVPLNELLERLQE 128

Bdellovibrio Bacteriovorus nucleoside diphosphate sugar hydrolase, and similar proteins; Bdellovibrio bacteriovorus nucleoside diphosphate sugar (NDPS) hydrolase Bd3179 has been shown to similarities to the Escherichia coli adenosine diphosphate ribose (ADPR) hydrolase and the guanosine diphosphate mannose (GDPM) hydrolase. It may have a role when Bdellovibrio degrades and metabolizes host cell. ADP-ribose pyrophosphatase (ADPRase) 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 654549455  19 IAREMLYSGFFsMELYRFRHRLFNGEMSgeiRREIFERGHAAVLLPFDPvRDEVVLVEQIRIAAYDVsespwLLEMVAGM 98
Cdd:cd24159    7 LSSRVVYKGGF-LKVHRDQVRLPDGSTS---TREYITHPGAVAVVPLLD-DGRVVMERQYRYPLKRV-----FLEFPAGK 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 654549455  99 IEEGESVEDVARREALEEAGLV------VGRTKPVLSYlaspggTSERLSIMVgevdattAEGIHGLA---DENEDIRVH 169
Cdd:cd24159   77 IDPGEDTLETAKRELLEETGYEaqewafLTTIHPAIGY------SNEHIEIYL-------ARGLTHVEqklDDGEFLEVV 143

                        170       180
                 ....*....|....*....|....*....
gi 654549455 170 VVSREQAYQWVEEGKIDNAASVIALQWLQ 198
Cdd:cd24159  144 EVSLAELLEMVLSGEITDVKTIIGLFWLQ 172

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 654549455  58 HAAVLLPFDPvRDEVVLVEQIRiaaydvSESPWLLEMVAGMIEEGESVEDVARREALEEAGLVVGRTKPVLSYLASPGGT 137
Cdd:cd02883    1 VAVGAVVFDD-EGRVLLVRRSD------GPGPGGWELPGGGVEPGETPEEAAVREVREETGLDVEVLRLLGVYEFPDPDE 73

                         90       100       110
                 ....*....|....*....|....*....|
gi 654549455 138 SERLSIMVGEVDATTAEGIHGLADENEDIR 167
Cdd:cd02883   74 GRHVVVLVFLARVVGGEPPPLDDEEISEVR 103

nudix hydrolase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 654549455  35 RFRHRLFNGEMSGEIRREIFERGHA-AVLLPFDPVRDE-VVLVEQIRiaaydVSESPWLLEMVAGMI--EEGESVeDVAR 110
Cdd:PLN03143 106 KFKADIIDKETGQKVPGIVFARGPAvAVLILLESEGETyAVLTEQVR-----VPVGKFVLELPAGMLddDKGDFV-GTAV 179

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 654549455 111 REALEEAGL---------VVGRTKPVLSY--LASPGGTSERLSIMV--GEVDATTAEGIHG----LADENEDIRVHVVSR 173
Cdd:PLN03143 180 REVEEETGIklkledmvdLTAFLDPSTGCrmFPSPGGCDEEISLFLyrGHVDKETIRQLQGketgLRDHGELIKVHVVPY 259

                        170       180
                 ....*....|....*....|.
gi 654549455 174 EQAYQWVEEGKidnAASVIAL 194
Cdd:PLN03143 260 RELWRMTADAK---VLMAIAL 277

NADH pyrophosphatase NudC, Nudix superfamily [Nucleotide transport and metabolism];

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 654549455  95 VAGMIEEGESVEDVARREALEEAGLVVGRtkpvLSYLAS-----PGgtserlSIMVG 146
Cdd:COG2816  187 LAGFVEPGETLEQAVRREVFEEVGVRVKN----VRYVGSqpwpfPS------SLMLG 233

NUDIX domain family NudE found in Escherichia coli, and similar proteins; The adenosine nucleotide hydrolase NudE protein in Escherichia coli is a NUDIX hydrolase family member active against ADP ribose, NADH, AP2A and AP3A33, and is classified as a hydrolase (E.C. 3.6.1.-) based on gene annotations. It is an 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 654549455  57 GHAAVL-LPFDPvRDEVVLVEQiriaaYDVSESPWLLEMVAGMIEEGESVEDVARREALEEAGLVVGRTKPVLSYLASPG 135
Cdd:cd24156    1 GRGAVMiVPILD-DDHLLLIRE-----YAAGTERYELGFPKGLIDPGETPEEAANRELKEEIGFGARQLTLLRELSLAPS 74

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 654549455 136 GTSERLSIMVGEvdATTAEGIHGlaDENEDIRVHVVSREQAYQWVEEGKIDNAASVIAL 194
Cdd:cd24156   75 YMSHKMHIVLAR--DLYPERLEG--DEPEPLEVVRWPLADLDELLADPDFTEARSIAAL 129

adenosine nucleotide hydrolase NudE; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 654549455   2 QKPEKLpvtfaknDVEIIARemlySGFF---SMELyRFRhrlfNGEmsgeirREIFER----GHAAVL-LPFDPvRDEVV 73
Cdd:PRK11762   6 QKPEIL-------NRETVAK----SRLFrveSVDL-EFS----NGV------ERVYERmrpsGRGAVMiVPILD-DDTLL 62

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 654549455  74 LVEQiriaaYDVSESPWLLEMVAGMIEEGESVEDVARREALEEAGLVVGRTKPVLSYLASPGGTSERLSIMVGEvD--AT 151
Cdd:PRK11762  63 LIRE-----YAAGTERYELGFPKGLIDPGETPLEAANRELKEEVGFGARQLTFLKELSLAPSYFSSKMNIVLAE-DlyPE 136

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|.
gi 654549455 152 TAEGihglaDENEDIRVHVVSREQAYQWVEEGKIDNAASVIAL----QWLQ 198
Cdd:PRK11762 137 RLEG-----DEPEPLEVVRWPLADLDELLARPDFSEARSVAALflarEWLK 182

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.

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                 ....*....|....*....|....*....|....*....|....*....|....
gi 654549455  68 VRDEVVLVEQIRIAAYDvsESPWLLemVAGMIEEGESVEDVARREALEEAGLVV 121
Cdd:cd04683    8 VRGDEVLLLRRANTGYD--DGWWHL--PAGHVEAGETVRAAAVREAKEELGVEI 57

MutT homolog-1 (MTH1); MutT homolog-1 (MTH1; EC 3.6.1.- ), also called 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
                 ....*....|....*....|....*....|.
gi 654549455  97 GMIEEGESVEDVARREALEEAGLVVGRTKPV 127
Cdd:cd03427   34 GKVEPGETIEEAAVRELEEEAGLTATELEKV 64

RNA pyrophosphohydrolase; The initiation of mRNA degradation often requires deprotection of its 5' end. In eukaryotes, the 5'-methylguanosine (cap) structure is principally removed by the NUDIX family decapping enzyme Dcp2, yielding a 5'-monophosphorylated RNA that is a substrate for 5' exoribonucleases. In bacteria, the 5'-triphosphate group of primary transcripts is also converted to a 5' monophosphate by a NUDIX protein called RNA pyrophosphohydrolase (RppH), allowing access to both endo- and 5' exoribonucleases. 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
                 ....*....|....*....|....*....|....*...
gi 654549455  93 EMVAGMIEEGESVEDVARREALEEAGLVVGRTKPVLSY 130
Cdd:cd04665   25 EFPGGKREPGETIEEAARRELYEETGAVIFELKPLGQY 62

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
                 ....*....|....*....|....*..
gi 654549455  95 VAGMIEEGESVEDVARREALEEAGLVV 121
Cdd:cd18886   30 VGGKLEPGESPEECAIREVFEETGLEL 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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 654549455  50 RREIFERG--HAAV-LLPFDPVRDEVVLveQIRIA-------AYDVSespwllemVAGMIEEGESVEDVARREALEEAGL 119
Cdd:cd04692   16 RSEVHRQGlwHRTVhVWLVNPEEGRLLL--QKRSAnkddfpgLWDIS--------AAGHIDAGETYEEAAVRELEEELGL 85

                 ..
gi 654549455 120 VV 121
Cdd:cd04692   86 TV 87

ADP-ribose pyrophosphatase; ADP-ribose pyrophosphatase (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. In humans, there are four distinct ADPRase activities, three putative cytosolic (ADPRase-I, -II, and -Mn) and a single mitochondrial enzyme (ADPRase-m). ADPRase-m is also known as NUDT9. It can be distinugished from the cytosolic ADPRase by a N-terminal target sequence unique to mitochondrial ADPRase. NUDT9 functions as a monomer.

                         10        20        30
                 ....*....|....*....|....*....|.
gi 654549455  97 GMIEEGESVEDVARREALEEAGLVVGRTKPV 127
Cdd:cd04673   33 GKVELGETLEDAALRELREETGLEAEVVGLL 63

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.

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                 ....*....|....*....|....*.
gi 654549455  96 AGMIEEGESVEDVARREALEEAGLVV 121
Cdd:cd04511   33 AGFMELGETTEQGAARETREEAGARV 58