Conserved Protein Domain Family
ATase

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cd06445: ATase 
Click on image for an interactive view with Cn3D
The DNA repair protein O6-alkylguanine-DNA alkyltransferase (ATase; also known as AGT, AGAT and MGMT) reverses O6-alkylation DNA damage by transferring O6-alkyl adducts to an active site cysteine irreversibly, without inducing DNA strand breaks. ATases are specific for repair of guanines with O6-alkyl adducts, however human ATase is not limited to O6-methylguanine, repairing many other adducts at the O6-position of guanine as well. ATase is widely distributed among species. Most ATases have N- and C-terminal domains. The C-terminal domain contains the conserved active-site cysteine motif (PCHR), the O6-alkylguanine binding channel, and the helix-turn-helix (HTH) DNA-binding motif. The active site is located near the recognition helix of the HTH motif. While the C-terminal domain of ATase contains residues that are necessary for DNA binding and alkyl transfer, the function of the N-terminal domain is still unknown. Removal of the N-terminal domain abolishes the activity of the C-terminal domain, suggesting an important structural role for the N-terminal domain in orienting the C-terminal domain for proper catalysis. Some ATase C-terminal domain homologs are either single-domain proteins that lack an N-terminal domain, or have a tryptophan substituted in place of the acceptor cysteine (i.e. the motif PCHR is replaced by PWHR). ATase null mutant mice are viable, fertile, and have a normal lifespan.
Statistics
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PSSM-Id: 119438
View PSSM: cd06445
Aligned: 378 rows
Threshold Bit Score: 50.5578
Threshold Setting Gi: 50842197
Created: 8-Jan-2008
Updated: 17-Jan-2013
Structure
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Program:
Drawing:
Aligned Rows:
 
active siteDNA binding
Conserved site includes 5 residues -Click on image for an interactive view with Cn3D
Feature 1:active site [active site]
Evidence:
  • Comment:The catalytic Tyr induces rotation of the 3' phosphate of the nucleotide to promote the flipping of the target nucleotide and alkylated guanine, transferring the O6-alkyl adduct to the active site Cys. The His, stabilized by Glu, acts as a general base to deprotonate Cys.

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                            #                                ## #                       
1YFH_A        94 FTRQVLWKLLkvvkFGEVISYQQLAALAGNp-kAARAVGGAMRGNpvp-ilIPCHRVVCssgAVGNYs------gGLAVK 165
gi 56404424   16 LYSYFYGLVKqi-pEGYVTTYGDLAQALGDp-iAARAVGYMLSINedp-dtIPCYRVVLhdgTVGNYth----plGPMEK 88
gi 86741627  571 RWTLMSRVLAai-pPGRWTSYSDVAEVIGS---HAVAVGAKLASAr----iSNAHRVLLl-nGSVSPdfrwpdpeRTDDP 641
gi 186681594 150 PYERFLDFIIki-pSGKVVTYKQIIKAIGVdnsYLRVIPTYLKKTsa--tnYPVHRILD---YKGYLi------tYVNQQ 217
gi 170289839  10 FQRILREALEqv-pYGEVTTFKIIAEALGDg-rAALAVRNECMRLskmdpdIPWWRVVSs--KLEPIp------gAEEKL 79
gi 56404387   19 LINELINLIEqi-pKGYVTTFKELAKALGDp-iATKFVAMYYKKA------PHWYRVVSs-nLIVSPm-------QKALL 82
gi 87310750   18 LPSDLQQRIAqi-pLGKVATYGRIAQSLGDr-lASRWIGDWLLRSpla-ttIAAHRVVRaggELGLFht-----gSSVDK 89
gi 78486537    6 FNEQCYALLEqv-pAGKVTTYKALAEALGTr--AYQAVGRAMNQNpnp-vvVPCHRVVNhngELGGYa------fGMARK 75
gi 45357632    4 FNEQCYDLIMqi-pRGKVTTYKIIAEALNTk--AYRAVGNAMKNNpki-ltVPCHRVVNsngYVGGYv------nGVEKK 73
gi 126464954  19 LYEAIYILTMli-pIGKVTTYKSIAKVLGV---HPRLVGIALKKNkkp-iiIPCHRVISsdgSIRGYsv-----gGKNVK 88

                 ....*...
Feature 1              # 
1YFH_A       166 EWLLAHEG 173
gi 56404424   89 VRRLRADG 96
gi 86741627  642 REILTAEG 649
gi 186681594 218 KDKLKTEG 225
gi 170289839  80 REEGGIER 87
gi 56404387   83 EKEVKIIG 90
gi 87310750   90 QRLLTAEG 97
gi 78486537   76 IELLTQEG 83
gi 45357632   74 IEILKNEG 81
gi 126464954  89 KKLLEIEG 96

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