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
                 ....*....|....*....|....*....|....*..
gi 499296655  34 AVLTIRAGvlQVLLVERGQEPYAGRWALPGGFVLPHE 70
Cdd:cd04691    5 GGVVVKEG--KVLLVKRAYGPGKGRWTLPGGFVEEGE 39

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 499296655  28 AVTVDLAVLTIRAGVLQVLLVERGQEPYAGRWALPGGFVLPHESAEAAARRELAEETGladLTGLHLEQLRTYSEPDRDP 107
Cdd:cd18873    2 SVTVDCVIFGFDDGELKVLLIKRKNEPFKGGWALPGGFVREDETLEDAARRELREETG---LKDIYLEQLGTFGDPDRDP 78

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 499296655 108 RMRVVSVAYTALLP-DPPEPHGGGDAAQAQWLRYNALGP-LAFDHDRILADAHE 159
Cdd:cd18873   79 RGRVISVAYLALVPeEDLAPKAGDDAAEARWFPVDELLPpLAFDHAEIIADALE 132

NUDIX domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 499296655   44 QVLLVERGQEPYAGRWALPGGFVLPHESAEAAARRELAEETGL-ADLTGLHLEQLRTYSEPDRDPRMRVVSVAYTALLPD 122
Cdd:pfam00293  16 RVLLVRRSKKPFPGWWSLPGGKVEPGETPEEAARRELEEETGLePELLELLGSLHYLAPFDGRFPDEHEILYVFLAEVEG 95

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 499296655  123 PPEPHGGGDAAQAQWLRYNAL--GPLAFDHDRILAD 156
Cdd:pfam00293  96 ELEPDPDGEVEEVRWVPLEELllLKLAPGDRKLLPW 131

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 499296655  28 AVTVDLAVLTIRAGVLQVLLVERGQEPYAGRWALPGGFVLPHESAEAAARRELAEETGladLTGLHLEQLRTYSEPDRDP 107
Cdd:cd18873    2 SVTVDCVIFGFDDGELKVLLIKRKNEPFKGGWALPGGFVREDETLEDAARRELREETG---LKDIYLEQLGTFGDPDRDP 78

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 499296655 108 RMRVVSVAYTALLP-DPPEPHGGGDAAQAQWLRYNALGP-LAFDHDRILADAHE 159
Cdd:cd18873   79 RGRVISVAYLALVPeEDLAPKAGDDAAEARWFPVDELLPpLAFDHAEIIADALE 132

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 499296655  28 AVTVDLAVLTIRagvLQVLLVERGQEPYAGRWALPGGFVLPHESAEAAARRELAEETGladLTGLHLEQLRTYSEPDrdp 107
Cdd:COG1051    6 KVAVDAVIFRKD---GRVLLVRRADEPGKGLWALPGGKVEPGETPEEAALRELREETG---LEVEVLELLGVFDHPD--- 76

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 499296655 108 RMRVVSVAYTALLPDpPEPHGGGDAAQAQWLRYNALGPLAF---DHDRI 153
Cdd:COG1051   77 RGHVVSVAFLAEVLS-GEPRADDEIDEARWFPLDELPELAFtpaDHEIL 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 499296655  44 QVLLVERGQEPYAGRWALPGGFVLPHESAEAAARRElaeetgLADLTGLHLEQLR-TYSEPD----RDPRMRVVSVAYTA 118
Cdd:cd04681   18 EILFVRRAKEPGKGKLDLPGGFVDPGESAEEALRRE------LREELGLKIPKLRyLCSLPNtylyKGITYKTCDLFFTA 91

                         90       100       110
                 ....*....|....*....|....*....|....
gi 499296655 119 LLPDPPEPH-GGGDAAQAQWLRYNALGP--LAFD 149
Cdd:cd04681   92 ELDEKPKLKkAEDEVAELEWLDLEEIEPekLAFP 125

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 499296655  167 YTCLATSFCPPEFTLGELQQVYETVWGTAL-DRPNFRRKVLATpGFVEQIpgAARLTGGRGKPAALYR 233
Cdd:pfam19368   1 YSPIAFDVLPELFTLNDLYQFYTTVLGENFsDYSNFRTRLLKL-GFLSDT--GKKVSRGAGRPASLYR 65

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 499296655  30 TVDLAVLTIRAGVLQVllvERGQEPYAGRWALPGGFVLPHESAEAAARRELAEETGL-ADLTGLHLeqLRTYSEPDRdpR 108
Cdd:cd04674    5 PVVVALLPVRDGLLVI---RRGIEPGHGELALPGGYIEYGETWQEAAVRELREETGVeADAAEVRL--FAVRSAPDG--T 77

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 499296655 109 MRVVsvaytALLPDPPEPHGGGDAAQ---AQWLRYNALGPLAF 148
Cdd:cd04674   78 LLIF-----GLLPERPVADLPPFAPTdeaTEWVVLTEPVELAF 115

ADP-ribose pyrophosphatase and similar proteins; 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 499296655  34 AVLTIRAGvlQVLLVERGQEPYAGRWALPGGFVLPHE 70
Cdd:cd04691    5 GGVVVKEG--KVLLVKRAYGPGKGRWTLPGGFVEEGE 39