1IRY,4N1U,4N1T,4C9W,5WS7,5HZX,6EHH,5MZF,3Q93,5ANS


Conserved Protein Domain Family
NUDIX_MTH1_Nudt1

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cd03427: NUDIX_MTH1_Nudt1 
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.
Statistics
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PSSM-Id: 467533
Aligned: 69 rows
Threshold Bit Score: 121.098
Created: 12-Sep-2005
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                                           #######################                    
1IRY_A       5 RLYTLVLVLQp-----qRVLLGMKKRgfgaGRWNGFGGKVQEGETIEDGARRELQEESGLTVda--lHKVGQIVFEFvge 77   Homo sapiens
ADH62975     2 TLCAEVFVLDrp---ngRMLLGRKKLglgaGNYQGFGGKLEPGETLAQCAVRELWEESGLKAkednlWYMAHLIFLFpnk 78   Meiothermus silv...
EGG20445     2 LRTNLCFFIDnss-tprRLLLGLKKKgfgkGRWNGIGGKKTDDETIDESAIRECVEEVGLKPtn--lVKRGELQYYYknq 78   Dictyostelium fa...
ADV24435    50 IEYSLVFVVDrq---tsKVLLGLKRRgmgiGLYNGYGGKPEPGESMLDCAVRELHEESGLVVnrfdlHYKGILLTSRpdp 126  Cryptococcus bac...
5WS7_A       5 RLYTLVLVLQp-----qRVLLGMKKRgfgaGRWNGFGGKVQEGETIEDGARRELQEESGLTVda--lHKVGQIVFEFvge 77   human
EFA85482  2322 KLVNLCLFIRnn---nkEILLGLKKRgfgvGKWDGCGGKVEPNESVEEGAIREAKEEFGLTPt----TIYSNPKYVGgp- 2393 Polysphondylium ...
ABY22563     4 APVTLLFLLRtqesgaqEVLLGLKKTgfgtGKIVGIGGHVEPGESAIEAAVREIAEETSIDVlpadlAYRGSVAFRFpah 83   Renibacterium sa...
ACL39510     4 AAVTLCFLLRdga-dgtQVLLGLKQTgfgrGKIVGIGGHVEPGETSVQAVIREVLEETGVVLqqgdlTDAGAVHFVFpar 82   Arthrobacter chl...
ACZ25336     2 KPTTLVFPIDek----nRILLGRKKRgfgaNKYNGFGGKLDDGESFRECAIRELYEESGLQGrvedlECVAAFDFQFpfd 77   Veillonella parv...
EFP57450     7 LETCLVLVTRtsd-gadEVLLGRKLRgfgrSRVVAPGGKIDAGESAQEAAARELEEETGLRAqt--lAPAGVLDFRFshd 83   Dermacoccus sp. ...
Feature 1                                                                                      
1IRY_A      78 -----peLMDVHVFCTdsIQGTPVesDEMRPCWFQLdqip---------fkdMWPDDSYWFPLLLqkk----------kf 133  Homo sapiens
ADH62975    79 ----pqwSQDVHVFRLehWEGEPQetEEMKPEWFDLktlp---------ltqMWDDVQYWLPQALega----------rp 135  Meiothermus silv...
EGG20445    79 ----khmNTHCTIYTIdmWTGDLIesDEMSPKWWNLdsdsnsdntdplpydlMWDDMKVWFPSFInsdfktatttptkft 154  Dictyostelium fa...
ADV24435   127 gpqheksLLRIHIYACtsWTGTPEttEEMEPKWIDIadlp---------lekMWPEARKYVPPLLqsil-------qdkl 190  Cryptococcus bac...
5WS7_A      78 -----peLMDVHVFATdsIQGTPVesDEMRPSWFQLdqip---------fkdMWPDDSYWFPLLLqkk----------kf 133  human
EFA85482  2394 -----meHLENHVFIVtdWSGELVetDEMQPKWFDLeregm-------pfksMWPDFEIWFNYLKdn-----------hf 2450 Polysphondylium ...
ABY22563    84 ----adwDMDAEVFIAldWTGEAResEEIAPQWYAVdalp---------aaqMWEDAGHWLPGLLsgp----------vq 140  Renibacterium sa...
ACL39510    83 ----pewDMETTLFTArtWTGDPQpsDEILPEWFRVdtlp---------vdrMWQDADHWLPVVLegg----------tv 139  Arthrobacter chl...
ACZ25336    78 ----eslTHVSYVYFLrtFTGTVEetDEMEPHWLEPnqip---------yehMWDGDRRWLPMLLegk----------kl 134  Veillonella parv...
EFP57450    84 d---ltqDMRAHVFIAsdALGAVQdsDEIAGRWVRQdgip---------yvkMWPDARHWVPRALagt----------lq 141  Dermacoccus sp. ...
Feature 1            
1IRY_A     134 HGYFKF 139  Homo sapiens
ADH62975   136 KLRFIY 141  Meiothermus silvanus DSM 9946
EGG20445   155 STNFYF 160  Dictyostelium fasciculatum
ADV24435   191 NTEMLL 196  Cryptococcus bacillisporus WM276
5WS7_A     134 HGYFKF 139  human
EFA85482  2451 KAKLDF 2456 Polysphondylium pallidum PN500
ABY22563   141 HFAVQL 146  Renibacterium salmoninarum ATCC 33209
ACL39510   140 NVVVTM 145  Arthrobacter chlorophenolicus A6
ACZ25336   135 KGPIVF 140  Veillonella parvula DSM 2008
EFP57450   142 HALFVY 147  Dermacoccus sp. Ellin185

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