1YFH,1T39,1QNT,1EH6,1EH7,1T38,1MGT,2G7H,1WRJ,1SFE


Conserved Protein Domain Family
ATase
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cd06445: ATase 
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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.
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Statistics
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PSSM-Id: 119438
Aligned: 378 rows
Threshold Bit Score: -1
Created: 8-Jan-2008
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
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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.
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Sequence Alignment
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Format: Row Display: Color Bits: Type Selection: 
Feature 1                            #                                ## #                       
1YFH_A        94 FTRQVLWKLLkvvkFGEVISYQQLAALAGNp-kAARAVGGAMRGNpvp-ilIPCHRVVCssgAVGNYs------gGLAVK 165 human
Q9HKY3        16 LYSYFYGLVKqi-pEGYVTTYGDLAQALGDp-iAARAVGYMLSINedp-dtIPCYRVVLhdgTVGNYth----plGPMEK 88  Thermoplasma ac...
YP_482027    571 RWTLMSRVLAai-pPGRWTSYSDVAEVIGS---HAVAVGAKLASAr----iSNAHRVLLl-nGSVSPdfrwpdpeRTDDP 641 Frankia sp. CcI3
YP_001864790 150 PYERFLDFIIki-pSGKVVTYKQIIKAIGVdnsYLRVIPTYLKKTsa--tnYPVHRILD---YKGYLi------tYVNQQ 217 Nostoc punctifo...
YP_001736655  10 FQRILREALEqv-pYGEVTTFKIIAEALGDg-rAALAVRNECMRLskmdpdIPWWRVVSs--KLEPIp------gAEEKL 79  Candidatus Kora...
Q74NK2        19 LINELINLIEqi-pKGYVTTFKELAKALGDp-iATKFVAMYYKKA------PHWYRVVSs-nLIVSPm-------QKALL 82  Nanoarchaeum eq...
ZP_01092877   18 LPSDLQQRIAqi-pLGKVATYGRIAQSLGDr-lASRWIGDWLLRSpla-ttIAAHRVVRaggELGLFht-----gSSVDK 89  Blastopirellula...
YP_392462      6 FNEQCYALLEqv-pAGKVTTYKALAEALGTr--AYQAVGRAMNQNpnp-vvVPCHRVVNhngELGGYa------fGMARK 75  Thiomicrospira ...
NP_987189      4 FNEQCYDLIMqi-pRGKVTTYKIIAEALNTk--AYRAVGNAMKNNpki-ltVPCHRVVNsngYVGGYv------nGVEKK 73  Methanococcus m...
YP_001040063  19 LYEAIYILTMli-pIGKVTTYKSIAKVLGV---HPRLVGIALKKNkkp-iiIPCHRVISsdgSIRGYsv-----gGKNVK 88  Staphylothermus...
Q9HKY3        16 LYSYFYGLVKqi-pEGYVTTYGDLAQALGDp-iAARAVGYMLSINedp-dtIPCYRVVLhdgTVGNYth----plGPMEK 88  Thermoplasma ac...
YP_482027    571 RWTLMSRVLAai-pPGRWTSYSDVAEVIGS---HAVAVGAKLASAr----iSNAHRVLLl-nGSVSPdfrwpdpeRTDDP 641 Frankia sp. CcI3
YP_001864790 150 PYERFLDFIIki-pSGKVVTYKQIIKAIGVdnsYLRVIPTYLKKTsa--tnYPVHRILD---YKGYLi------tYVNQQ 217 Nostoc punctifo...
YP_001736655  10 FQRILREALEqv-pYGEVTTFKIIAEALGDg-rAALAVRNECMRLskmdpdIPWWRVVSs--KLEPIp------gAEEKL 79  Candidatus Kora...
Q74NK2        19 LINELINLIEqi-pKGYVTTFKELAKALGDp-iATKFVAMYYKKA------PHWYRVVSs-nLIVSPm-------QKALL 82  Nanoarchaeum eq...
ZP_01092877   18 LPSDLQQRIAqi-pLGKVATYGRIAQSLGDr-lASRWIGDWLLRSpla-ttIAAHRVVRaggELGLFht-----gSSVDK 89  Blastopirellula...
YP_392462      6 FNEQCYALLEqv-pAGKVTTYKALAEALGTr--AYQAVGRAMNQNpnp-vvVPCHRVVNhngELGGYa------fGMARK 75  Thiomicrospira ...
NP_987189      4 FNEQCYDLIMqi-pRGKVTTYKIIAEALNTk--AYRAVGNAMKNNpki-ltVPCHRVVNsngYVGGYv------nGVEKK 73  Methanococcus m...
YP_001040063  19 LYEAIYILTMli-pIGKVTTYKSIAKVLGV---HPRLVGIALKKNkkp-iiIPCHRVISsdgSIRGYsv-----gGKNVK 88  Staphylothermus...

Feature 1              # 
1YFH_A       166 EWLLAHEG 173 human
Q9HKY3        89 VRRLRADG 96  Thermoplasma acidophilum DSM 1728
YP_482027    642 REILTAEG 649 Frankia sp. CcI3
YP_001864790 218 KDKLKTEG 225 Nostoc punctiforme PCC 73102
YP_001736655  80 REEGGIER 87  Candidatus Korarchaeum cryptofilum OPF8
Q74NK2        83 EKEVKIIG 90  Nanoarchaeum equitans Kin4-M
ZP_01092877   90 QRLLTAEG 97  Blastopirellula marina DSM 3645
YP_392462     76 IELLTQEG 83  Thiomicrospira crunogena XCL-2
NP_987189     74 IEILKNEG 81  Methanococcus maripaludis S2
YP_001040063  89 KKLLEIEG 96  Staphylothermus marinus F1
Q9HKY3        89 VRRLRADG 96  Thermoplasma acidophilum DSM 1728
YP_482027    642 REILTAEG 649 Frankia sp. CcI3
YP_001864790 218 KDKLKTEG 225 Nostoc punctiforme PCC 73102
YP_001736655  80 REEGGIER 87  Candidatus Korarchaeum cryptofilum OPF8
Q74NK2        83 EKEVKIIG 90  Nanoarchaeum equitans Kin4-M
ZP_01092877   90 QRLLTAEG 97  Blastopirellula marina DSM 3645
YP_392462     76 IELLTQEG 83  Thiomicrospira crunogena XCL-2
NP_987189     74 IEILKNEG 81  Methanococcus maripaludis S2
YP_001040063  89 KKLLEIEG 96  Staphylothermus marinus F1

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