UDP-glucose pyrophosphatase; UDP-glucose pyrophosphatase (UGPPase) (EC 3.6.1.45; also known as NUDIX (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 941355814  25 YRQDGVQKSWDFMKTHDSVTILMFNSSRRSLVLVKQFRPG---SLTAVNQDQPQELQQALPGSAGVMVELCAGIVDQPgL 101
Cdd:cd18887    1 YKQNGKKKTWDFVKSHDSVAILLYNKTRDAFVLVKQFRPAvyaSQVRAAERNGGKDTEKYPPELGYTYELCAGLVDKD-K 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 941355814 102 SLEEAACKEAWEECGYRLVPTDLRRVATYMSGVGLTSSRQTMFYAEVTDAQRGGPGGGLAEEGELIEVIHLNLDDAQAFA 181
Cdd:cd18887   80 SLEEIAQEEILEECGYDVPLEDLEKITSFRSGVGTSGSRQTLFYAEVTDDMKVSEGGGVEEEGEMIEVVELPVEEAKEFI 159

                        170
                 ....*....|....*....
gi 941355814 182 DNPDIPKTLGVIYAISWFF 200
Cdd:cd18887  160 FDEEIPKPPGLLFALLWFL 178

UDP-glucose pyrophosphatase; UDP-glucose pyrophosphatase (UGPPase) (EC 3.6.1.45; also known as NUDIX (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 941355814  25 YRQDGVQKSWDFMKTHDSVTILMFNSSRRSLVLVKQFRPG---SLTAVNQDQPQELQQALPGSAGVMVELCAGIVDQPgL 101
Cdd:cd18887    1 YKQNGKKKTWDFVKSHDSVAILLYNKTRDAFVLVKQFRPAvyaSQVRAAERNGGKDTEKYPPELGYTYELCAGLVDKD-K 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 941355814 102 SLEEAACKEAWEECGYRLVPTDLRRVATYMSGVGLTSSRQTMFYAEVTDAQRGGPGGGLAEEGELIEVIHLNLDDAQAFA 181
Cdd:cd18887   80 SLEEIAQEEILEECGYDVPLEDLEKITSFRSGVGTSGSRQTLFYAEVTDDMKVSEGGGVEEEGEMIEVVELPVEEAKEFI 159

                        170
                 ....*....|....*....
gi 941355814 182 DNPDIPKTLGVIYAISWFF 200
Cdd:cd18887  160 FDEEIPKPPGLLFALLWFL 178

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 941355814  41 DSVTILMFNSSRRsLVLVKQFRPGSltavnqdqpqelqqalpgsAGVMVELCAGIVDqPGLSLEEAACKEAWEECGYRlv 120
Cdd:COG0494   14 PAVVVVLLDDDGR-VLLVRRYRYGV-------------------GPGLWEFPGGKIE-PGESPEEAALRELREETGLT-- 70

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 941355814 121 PTDLRRVATYMSGvGLTSSRQTMFYAEVTDAqrgGPGGGLAEEGELIEVIHLNLDDAQAFADNPDIPKTL 190
Cdd:COG0494   71 AEDLELLGELPSP-GYTDEKVHVFLARGLGP---GEEVGLDDEDEFIEVRWVPLDEALALVTAGEIAKTL 136

NUDIX domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 941355814   38 KTHDSVTILMFNSSRRsLVLVKQFRPGsltavnqdqpqelqqaLPGsagvMVELCAGIVDqPGLSLEEAACKEAWEECGY 117
Cdd:pfam00293   1 KRRVAVGVVLLNEKGR-VLLVRRSKKP----------------FPG----WWSLPGGKVE-PGETPEEAARRELEEETGL 58

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 941355814  118 RLVPTDLRRVATYMSGVGLTSSRQTM----FYAEVTDAQRGGPGgglaeeGELIEVIHLNLDDAQAFADNPDIPKTL 190
Cdd:pfam00293  59 EPELLELLGSLHYLAPFDGRFPDEHEilyvFLAEVEGELEPDPD------GEVEEVRWVPLEELLLLKLAPGDRKLL 129

UDP-glucose pyrophosphatase; UDP-glucose pyrophosphatase (UGPPase) (EC 3.6.1.45; also known as NUDIX (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 941355814  25 YRQDGVQKSWDFMKTHDSVTILMFNSSRRSLVLVKQFRPG---SLTAVNQDQPQELQQALPGSAGVMVELCAGIVDQPgL 101
Cdd:cd18887    1 YKQNGKKKTWDFVKSHDSVAILLYNKTRDAFVLVKQFRPAvyaSQVRAAERNGGKDTEKYPPELGYTYELCAGLVDKD-K 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 941355814 102 SLEEAACKEAWEECGYRLVPTDLRRVATYMSGVGLTSSRQTMFYAEVTDAQRGGPGGGLAEEGELIEVIHLNLDDAQAFA 181
Cdd:cd18887   80 SLEEIAQEEILEECGYDVPLEDLEKITSFRSGVGTSGSRQTLFYAEVTDDMKVSEGGGVEEEGEMIEVVELPVEEAKEFI 159

                        170
                 ....*....|....*....
gi 941355814 182 DNPDIPKTLGVIYAISWFF 200
Cdd:cd18887  160 FDEEIPKPPGLLFALLWFL 178

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 941355814  41 DSVTILMFNSSRRSLVLVKQFRPGSLtavnqdqpqelqqaLPGSAGVMVELCAGIVDqpGLSLEEAACKEAWEECGYRLv 120
Cdd:cd24157    5 DAAAVLLYDPKRKTVVLVRQFRAPAY--------------LGGGDGWLIEACAGLLD--GDDPEDCIRREAEEETGYRL- 67

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 941355814 121 pTDLRRVAT-YMSGvGLTSSRQTMFYAEVTDAQRGGPGGGLAEEGELIEVIHLNLDDA 177
Cdd:cd24157   68 -GDLEKVFTaYSSP-GIVTERIHLFIAEYSSADRVGAGGGLAEEGEDIEVLELPLDEA 123

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 941355814  39 THDSVTILMFNSSRRsLVLVKQFRPgsltAVNQdqpqelqqalpgsagVMVELCAGIVDqPGLSLEEAACKEAWEECGYR 118
Cdd:cd03424    1 HPGAVAVLAITDDGK-VVLVRQYRH----PVGR---------------VLLELPAGKID-PGEDPEEAARRELEEETGYT 59

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 941355814 119 lvPTDLRRVATYMSGVGLTSSRQTMFYAEVTDAQRGGPGgglaEEGELIEVIHLNLDDAQAFADNPDI--PKTlgvIYAI 196
Cdd:cd03424   60 --AGDLELLGSFYPSPGFSDERIHLFLAEDLTPVSEQAL----DEDEFIEVVLVPLEEALEMIEDGEItdAKT---LAAL 130

                 ...
gi 941355814 197 SWF 199
Cdd:cd03424  131 LLA 133

GDP-mannose pyrophosphatase NudK; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 941355814  44 TILMFNSSRRSLVLVKQFRPGSLTAVNQDqpqelqqalpgsaGVMVELCAGIVDQPglslEEAAC--KEAWEECGYRLvp 121
Cdd:PRK15009  49 TILLYNAKKKTVVLIRQFRVATWVNGNES-------------GQLIETCAGLLDND----EPEVCirKEAIEETGYEV-- 109

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 941355814 122 TDLRRV-ATYMSGVGLTSSRQtMFYAEVTDAQRGGPGGGLaeEGELIEVIHLNLDDA 177
Cdd:PRK15009 110 GEVRKLfELYMSPGGVTELIH-FFIAEYSDSQRANAGGGV--EDEDIEVLELPFSQA 163

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 941355814  90 ELCAGIVDqPGLSLEEAACKEAWEECGYRLVPTDLRRVATYMSGVGLTSSRQTMFYAEVTDAQRGGPGGGLAEEGELI 167
Cdd:cd02883   29 ELPGGGVE-PGETPEEAAVREVREETGLDVEVLRLLGVYEFPDPDEGRHVVVLVFLARVVGGEPPPLDDEEISEVRWV 105

NUDIX domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 941355814   38 KTHDSVTILMFNSSRRsLVLVKQFRPGsltavnqdqpqelqqaLPGsagvMVELCAGIVDqPGLSLEEAACKEAWEECGY 117
Cdd:pfam00293   1 KRRVAVGVVLLNEKGR-VLLVRRSKKP----------------FPG----WWSLPGGKVE-PGETPEEAARRELEEETGL 58

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 941355814  118 RLVPTDLRRVATYMSGVGLTSSRQTM----FYAEVTDAQRGGPGgglaeeGELIEVIHLNLDDAQAFADNPDIPKTL 190
Cdd:pfam00293  59 EPELLELLGSLHYLAPFDGRFPDEHEilyvFLAEVEGELEPDPD------GEVEEVRWVPLEELLLLKLAPGDRKLL 129

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        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 941355814  90 ELCAGIVdQPGLSLEEAACKEAWEECGYrlVPTDLRRVATY-MSGVGLTSSRqTMFYAEVTD 150
Cdd:cd04665   25 EFPGGKR-EPGETIEEAARRELYEETGA--VIFELKPLGQYsVHGKGQEFFG-AVYYAEVKS 82

Adp-ribose pyrophosphatase (ADPRase) found in Thermus thermophilus, and similar proteins; ADP-ribose pyrophosphatase (ADPRase) such as found in extreme thermophile Thermus thermophilus (TtADPRase) catalyzes the hydrolysis of ADPR to AMP and ribose 5'-phosphate in the presence of Mg2+ and Zn2+ ions. 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 941355814  34 WDFMKTHDSVTILMFNSSRrsLVLVKQFRPgsltAVNQDQpqelqqalpgsagvmVELCAGIVDqPGLSLEEAACKEAWE 113
Cdd:cd24160   15 YEIVEHADAVAVLALREGR--MLFVRQMRP----AVGAAT---------------LEIPAGLID-PGETPEEAARRELAE 72

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 941355814 114 ECGYRlvpTDLRRVATYMSGVGLTSSRQTMFYAEVTDAQRGGPggglaEEGELIEVI----HLNLDDAQAFADNPDIPKT 189
Cdd:cd24160   73 ETGLS---GDLTYLTRFYVSPGFCDEKLHVFLAENLREVEAHP-----DEDEAIEVVwmrpEEVLERLRRGEVEFSATTL 144

                 ....*..
gi 941355814 190 LGVIYAI 196
Cdd:cd24160  145 VGVLYYH 151

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 941355814  80 ALPGsagvmvelcaGIVdQPGLSLEEAACKEAWEECGyrLVPTDLRRVATYMSGvgltSSRQTMFYAEVTDAQRGGPG 157
Cdd:cd04667   24 LLPG----------GKI-EPGESPLEAAIRELKEETG--LAALSLLYLFEHEGP----HKLHHVFLAEAPDGGRPRPG 84