4KYX,5GP0,5WY6,5BON,6YPB,5GP0,6DBY,6FL4,5WWD


Conserved Protein Domain Family
NUDIX_MTH2_Nudt15

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cd04678: NUDIX_MTH2_Nudt15 
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.
Statistics
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PSSM-Id: 467561
Aligned: 82 rows
Threshold Bit Score: 94.5521
Created: 6-Dec-2006
Updated: 27-Apr-2023
Structure
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Program:
Drawing:
Aligned Rows:
 
Conserved site includes 23 residues -Click on image for an interactive view with Cn3D
Feature 1:NUDIX motif [structural motif]
Evidence:
  • Comment:G[X5]E[X7]REUXEEXGU, where U is a bulky aliphatic residue (usually Ile, Leu, or Val).
  • Comment:The NUDIX motif contains many of the active site residues of NUDIX hydrolases.

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                                        #######################                      
4KYX_A     13 PRIGIGILIFNnrnEILLGKRIss-hgESSYAPAGGHLEFGETFEECAIREVLEETNLIIen--pQFIAVTNDif--ekE 87  Rickettsia felis U...
5GP0_E     10 PRVAVVVFILNg-nSILLGRRRss-igNSTFALPGGHLEFGESFEECAAREVMEETGLKIek--mKLLTVTNNvfkeapT 85  thale cress
CAM64414    8 PHPGIGCFVVRn-gRFLMGRRHga-hgAGTWSVPGGWIEWGESPEAAAIREVREETGMLVvd--aRVAGATTTsh---pE 80  Mycobacterium absc...
EHJ94735   11 PVIGVGAILVRpdgAVLLGYRDkp-geSPSWCLPGGHVDAGESFKTAAVREIAEETSISElq-rpQLLAITQNl----nS 84  Halomonas bolivien...
EGX60630  245 AALGVGVIVQGa-dGVLLGRHR-----RGTWELAGGSVEPGESFAEAAVRELYEEAGLLAdpggaRVLGTLLDq----vG 314 Streptomyces sp. C...
ABX05959   34 APAGVAAVIQNdfgEVLLVRRAgt-frPGLWCLPCGYLEHDEEMRQGLAREVLEETGLQAei--gEVIAVHSNld---rE 107 Herpetosiphon aura...
EHQ90939   37 PAVGVAAIIIRd-kKILLGRRNss--yRDMWCIPCGYVEYYEDAREALIREIKEETNLEIkl--gTVFDIHSNfh---nP 108 Desulfosporosinus ...
EJN14484   31 PAPIIAVLVVEg-dKFLLCRRKpdtleGGKWCLPCGYIEFHEDYLTAARREVKEETGLEIei--aALLGVASNfl---rP 104 Bradyrhizobium sp....
ADW19139   54 PHPGITIIIRSregKVLIGRRSersryGGRWCLPGGYIEYEESFIDTAHREVAEETGLKIri--dGIVNVVSNhl---dD 128 Desulfobulbus prop...
ACL04574   37 PTVGVAVIVMEk--GRLLLVKRkg-syEGMWCIPCGHLEWDEDVREGARREIFEETGLEVri--gPVFDALSNfh---dD 108 Desulfatibacillum ...
Feature 1                                                                    
4KYX_A     88 QKHYVSIFLKAHCLNEhel-qnlEPHKVENWQWFALDNLPs-----------nLFLPLKRLIE 138 Rickettsia felis URRWXCal2
5GP0_E     86 PSHYVSVSIRAVLVDPsqepknmEPEKCEGWDWYDWENLPk-----------pLFWPLEKLFG 137 thale cress
CAM64414   81 GMCSVTLWVVARWVSGepv--vmEPDKYAEHRWYGLDEALpa----------pLFEVWEDLLG 131 Mycobacterium abscessus ATCC 19977
EHJ94735   85 AASVVTGAVLANVEQDaea-lvlEPDVFTQWRWFSPGAFPt-----------pLFPASQAVLA 135 Halomonas boliviensis LC1
EGX60630  315 DIVPVTVPVLVTTWSGtp---qqREEAVGSWRFWPLAALPq-----------pLFVPSAQCLT 363 Streptomyces sp. CCNWNQ0016
ABX05959  108 PPYPLGVWLRATVSGGnl----qAGGDADLAQFFALDQLPplafnhdalvlaqLQQPADASVA 166 Herpetosiphon aurantiacus ATCC 23779
EHQ90939  109 AQHTVGIWFLAEAYQGdi----aPGDDIEALDFFSSAEIKaqn-------ivlAFPTDIKVLD 160 Desulfosporosinus youngiae DSM 17734
EJN14484  105 DIHTLAVAVLASPVGGam----cPGDDVDQLEWLSLADELps----------fAFSADRHMVE 153 Bradyrhizobium sp. YR681
ADW19139  129 LHHTLVVVLTGQQSGGil----rPGDDLTALRWIDGEQHKei---------gyAFEADRSIVD 178 Desulfobulbus propionicus DSM 2032
ACL04574  109 RRHTVGVWFWGKKIGGrl----aPGSDALDARFFSLDELPh-----------nLAFPTDQAVC 156 Desulfatibacillum aliphaticivorans

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