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
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2676810245   1 MPGLSIDNLIFgldHGQLKILLVKHSVGPGKGHWALPGGFISMKENLRDAASRLLKSLTGVE 62
Cdd:cd03430    13 TPLVSIDLIIR---NEDGEILLGKRNNRPAQGYWFVPGGRILKNETLDDAFKRIAREELGLE 71

bifunctional NMN adenylyltransferase/ADP-ribose pyrophosphatase and similar proteins; Bacterial NadM-Nudix is a bifunctional enzyme containing a nicotinamide mononucleotide (NMN) adenylyltransferase (NMNAT) and an ADP-ribose pyrophosphatase (ADPRase) domain. NMNAT was initially identified as an NAD+ synthase that catalyzes the reversible conversion of NMN to NAD+ in the final step of both the de novo biosynthesis and salvage pathways in most organisms across all three kingdoms of life ADPRase is a member of the NUDIX family proteins, catalyzes the metal-induced and concerted general acid-base hydrolysis of ADP ribose (ADPR) into AMP and ribose-5'-phosphate (R5P). Additional members in this cd include bacterial transcriptional regulator, NrtR, which represses the transcription of NAD biosynthetic genes in vitro and adenosine diphosphate ribose (ADPR), as well as NadQ, a NUDIX-like ATP-responsive regulator of NAD biosynthesis. Members of the NUDIX hydrolase superfamily catalyze the hydrolysis of NUcleoside DIphosphates linked to other moieties, X. Enzymes belong to this superfamily requires a divalent cation, such as Mg2+ or Mn2+ for their activity and contain a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, U=I, L or V) which functions as 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 _ "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 2676810245   2 PGLSIDNLIFGLDHGQLKILLVKHSVGPGKGHWALPGGFISMKENLRDAASRLLKSLTGVEDLYLEQLKTFGRVDRFPSE 81
Cdd:cd18873     1 PSVTVDCVIFGFDDGELKVLLIKRKNEPFKGGWALPGGFVREDETLEDAARRELREETGLKDIYLEQLGTFGDPDRDPRG 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 2676810245  82 RVVTVAYYALVSAEDYILVAGRDATDAEWFEVND-LPELIYDHAEIVEY 129
Cdd:cd18873    81 RVISVAYLALVPEEDLAPKAGDDAAEARWFPVDElLPPLAFDHAEIIAD 129

bifunctional nicotinamide-nucleotide adenylyltransferase/Nudix hydroxylase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2676810245  20 ILLVKHSVGPGKGHWALPGGFISMKENLRDAASRLLKSLTGVeDLYLEQLK-------TFGRVDRFPSERVVTVAYY-AL 91
Cdd:PRK05379  216 VLLVRRRAEPGKGLWALPGGFLEQDETLLDACLRELREETGL-KLPEPVLRgsirdqqVFDHPGRSLRGRTITHAFLfEF 294

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 2676810245  92 VSAEDYILVAGRDATDAEWFEVNDL---PELIY-DHAEIVEY 129
Cdd:PRK05379  295 PAGELPRVKGGDDADKARWVPLAELlamRDRMFeDHFQIITH 336

bifunctional NMN adenylyltransferase/ADP-ribose pyrophosphatase and similar proteins; Bacterial NadM-Nudix is a bifunctional enzyme containing a nicotinamide mononucleotide (NMN) adenylyltransferase (NMNAT) and an ADP-ribose pyrophosphatase (ADPRase) domain. NMNAT was initially identified as an NAD+ synthase that catalyzes the reversible conversion of NMN to NAD+ in the final step of both the de novo biosynthesis and salvage pathways in most organisms across all three kingdoms of life ADPRase is a member of the NUDIX family proteins, catalyzes the metal-induced and concerted general acid-base hydrolysis of ADP ribose (ADPR) into AMP and ribose-5'-phosphate (R5P). Additional members in this cd include bacterial transcriptional regulator, NrtR, which represses the transcription of NAD biosynthetic genes in vitro and adenosine diphosphate ribose (ADPR), as well as NadQ, a NUDIX-like ATP-responsive regulator of NAD biosynthesis. Members of the NUDIX hydrolase superfamily catalyze the hydrolysis of NUcleoside DIphosphates linked to other moieties, X. Enzymes belong to this superfamily requires a divalent cation, such as Mg2+ or Mn2+ for their activity and contain a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, U=I, L or V) which functions as 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 _ "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 2676810245   2 PGLSIDNLIFGLDHGQLKILLVKHSVGPGKGHWALPGGFISMKENLRDAASRLLKSLTGVEDLYLEQLKTFGRVDRFPSE 81
Cdd:cd18873     1 PSVTVDCVIFGFDDGELKVLLIKRKNEPFKGGWALPGGFVREDETLEDAARRELREETGLKDIYLEQLGTFGDPDRDPRG 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 2676810245  82 RVVTVAYYALVSAEDYILVAGRDATDAEWFEVND-LPELIYDHAEIVEY 129
Cdd:cd18873    81 RVISVAYLALVPEEDLAPKAGDDAAEARWFPVDElLPPLAFDHAEIIAD 129

AraR C-terminal winged HTH domain; This entry represents the C-terminal DNA-binding domain of AraR proteins which are involved in regulating Arabinose utilization. This domain has a winged helix-turn-helix structure.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2676810245 140 HEPIGFNLLPEKFTLLQLQELYEAILGVKL-DKPNFRRKMLKMNLLTPCNEKQKGVPHRAANLFRFDADAYYRLAEKGFS 218
Cdd:pfam19368   1 YSPIAFDVLPELFTLNDLYQFYTTVLGENFsDYSNFRTRLLKLGFLSDTGKKVSRGAGRPASLYRFDAEAFAPLKDKPLV 80

                  .
gi 2676810245 219 F 219
Cdd:pfam19368  81 F 81

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 2676810245  15 HGQLKILLVKHSVGPGKGHWALPGGFISMKENLRDAASRLLKSLTGVEDLYLEQLKTFGRVDRFPSERVVTVAYYALVSA 94
Cdd:cd02883     9 DDEGRVLLVRRSDGPGPGGWELPGGGVEPGETPEEAAVREVREETGLDVEVLRLLGVYEFPDPDEGRHVVVLVFLARVVG 88

                          90
                  ....*....|....*..
gi 2676810245  95 EDYILVAGRDATDAEWF 111
Cdd:cd02883    89 GEPPPLDDEEISEVRWV 105

NUDIX domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2676810245   1 MPGLSIDNLIFGldhGQLKILLVKHSVGPGKGHWALPGGFISMKENLRDAASRLLKSLTGVE----DLYLEQLKTFGRVD 76
Cdd:pfam00293   1 KRRVAVGVVLLN---EKGRVLLVRRSKKPFPGWWSLPGGKVEPGETPEEAARRELEEETGLEpellELLGSLHYLAPFDG 77

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 2676810245  77 RFPSERVVTVAYYALVSAEDyILVAGRDATDAEWFEVNDL--PELIYDHAEIVEY 129
Cdd:pfam00293  78 RFPDEHEILYVFLAEVEGEL-EPDPDGEVEEVRWVPLEELllLKLAPGDRKLLPW 131

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 2676810245  19 KILLVKHSVGPGKGHWALPGGFISMKENLRDAASRLLKSLTGVEdlyLEQLKTFGrvdRFPSE--------RVVTVAYYA 90
Cdd:cd04681    18 EILFVRRAKEPGKGKLDLPGGFVDPGESAEEALRRELREELGLK---IPKLRYLC---SLPNTylykgityKTCDLFFTA 91

                          90       100
                  ....*....|....*....|....*..
gi 2676810245  91 LVSAEDYILVAGRDATDAEWFEVNDLP 117
Cdd:cd04681    92 ELDEKPKLKKAEDEVAELEWLDLEEIE 118

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 2676810245  19 KILLVKHSVGPGKGHWALPGGFISMKENLRDAASRLLKSLTGVEDLYLEQLKTFGRVDRFPSERVVTVAYYALVSAEDYI 98
Cdd:cd04679    14 RLLLVLRLRAPEAGHWGLPGGKVDWLETVEDAVRREILEELGLEIELTRLLCVVDQIDAADGEHWVAPVYLAEIFSGEPR 93

                          90       100
                  ....*....|....*....|
gi 2676810245  99 LVAGRDATDAEWFEVNDLPE 118
Cdd:cd04679    94 LMEPEKHGGIGWFALDALPQ 113

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 2676810245  19 KILLVKHSVGPGKGHWALPGGFISMKENLRDAASRLLKSLTGVEdlyLEQLKTFGRV-DRFPSERV--VTVAYYA-LVSA 94
Cdd:cd04678    15 KVLLGRRKGSHGAGTWALPGGHLEFGESFEECAAREVLEETGLE---IRNVRFLTVTnDVFEEEGKhyVTIFVLAeVDDG 91

                          90       100
                  ....*....|....*....|....*
gi 2676810245  95 EDYILVAGRDATDAEWFEVNDLPEL 119
Cdd:cd04678    92 EPEENMEPDKCEGWEWFSWDELPPL 116

GDP-mannose glycosyl hydrolase; GDP-mannose glycosyl hydrolase, also known as GDP-mannose mannosyl hydrolase/GDPMH, is a member of the NUDIX hydrolase superfamily. This class of enzymes is unique from other members of the superfamily in two aspects. First, it contains a modified NUDIX signature sequence. The slight changes to the conserved sequence motif, GX5EX7REUXEEXGU, where U = I, L or V), are believed to contribute to the removal of all magnesium binding sites but one, retaining only the metal site that coordinates the pyrophosphate of the substrate. Secondly, it is not a pyrophosphatase that substitutes at a phosphorus; instead, it hydrolyzes nucleotide sugars such as GDP-mannose to GDP and mannose, cleaving the phosphoglycosyl bond by substituting at a carbon position. GDP-mannose provides mannosyl components for cell wall synthesis and is required for the synthesis of other glycosyl donors (such as GDP-fucose and colitose) for the cell wall. The importance of GDP-sugar hydrolase activities is thus closely related to the regulation of cell wall biosynthesis. Enzymes in this family are believed to regulate the concentration of GDP-mannose and GDP-glucose in the bacterial cell wall.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2676810245   1 MPGLSIDNLIFgldHGQLKILLVKHSVGPGKGHWALPGGFISMKENLRDAASRLLKSLTGVE 62
Cdd:cd03430    13 TPLVSIDLIIR---NEDGEILLGKRNNRPAQGYWFVPGGRILKNETLDDAFKRIAREELGLE 71

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
                  ....*....|....*....|....*....|....*
gi 2676810245  19 KILLVKHSVGPGKGHWALPGGFISMKENLRDAASR 53
Cdd:cd04511    14 KVLLCRRAIEPRKGYWTLPAGFMELGETTEQGAAR 48

NADH pyrophosphatase; NADH pyrophosphatase, also known as NUDIX (nucleoside diphosphate linked moiety X)) motif 13/Nudt13, is thought to have NADH pyrophosphatase activity, be involved in NADH metabolic process and NADP catabolic process, catalyzing the cleavage of NADH into reduced nicotinamide mononucleotide (NMNH) and AMP, and located in mitochondrion. Like other members of the NUDIX family, it requires a divalent cation, such as Mg2+ or Mn2+, for activity. Members of this family are also recognized by 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. A block of 8 conserved amino acids downstream of the NUDIX motif is thought to give NADH pyrophosphatase its specificity for NADH. NADH pyrophosphatase forms a dimer.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2676810245  15 HGQLKILLVKHSVGPgKGHWALPGGFISMKENLRDAASRLLKSLTGVedlyleqlktfgRVDR--------FPSERVVTV 86
Cdd:cd03429    10 NGEDKILLARQPRWP-PGRYSLLAGFVEPGETLEEAVRREVKEEVGL------------RVKNvryvgsqpWPFPSSLML 76

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 2676810245  87 AYYALVSAEDyILVAGRDATDAEWFEVNDLPELIY 121
Cdd:cd03429    77 GFTAEADSGE-ITVDDDELEDARWFSRDELPEALF 110

CDP-choline pyrophosphatase; CDP-choline pyrophosphatase catalyzes the hydrolysis of CDP-choline to produce CMP and phosphocholine. 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 2676810245  19 KILLVKHSVgpgKGHWALPGGFISMKENLRDAASRLLKSLTGVEdlyLEQLKTFGRVDRF-----PSERVVTVAYYaLVS 93
Cdd:cd18890    15 EILLVKEKE---DGKWTLPGGWADVGYTPTEVAAKEVEEETGLE---VSPKKLLAILDKRkhphpPQPTYVYKLFI-LCE 87

                          90       100
                  ....*....|....*....|....*....
gi 2676810245  94 AEDYILVAGRDATDAEWFEVNDLPELIYD 122
Cdd:cd18890    88 IEGGELKPSFETGEVRFFSENELPELSTD 116

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
                  ....*....|....*....|....*....|....*....|...
gi 2676810245  19 KILLVKHSvgpgKGHWALPGGFISMKENLRDAASRLLKSLTGV 61
Cdd:cd04667    12 RILLVARR----GGRWLLPGGKIEPGESPLEAAIRELKEETGL 50

UDP-X diphosphatase; UDP-X diphosphatase hydrolyzes UDP-N-acetylmuramic acid and UDP-N-acetylmuramoyl-L-alanine, the last step of the Mur pathway of peptidoglycan biosynthesis. 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 2676810245  19 KILLVKHSvgpGKGHWALPGGF----ISMKENLRdaasRLLKSLTGVeDLYLEQLKTFGRVDRFpSERVVTVAYYALV-- 92
Cdd:cd18891    14 KVLLVQDK---HTKEWALPGGFaevgLSPKENIL----KEVKEETGL-HVEVERLLAVFDTDLR-QDIPQSFQYYKFIfa 84

                          90       100
                  ....*....|....*....|....*...
gi 2676810245  93 -SAEDYILVAGRDATDAEWFEVNDLPEL 119
Cdd:cd18891    85 cKILDGEFQENSETSDLQYFSLDQLPNL 112