ALKA_MYCTO
ID ALKA_MYCTO Reviewed; 496 AA.
AC P9WJW2; L0T913; Q10630;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 47.
DE RecName: Full=Probable bifunctional transcriptional activator/DNA repair enzyme AlkA;
DE AltName: Full=Regulatory protein AlkA;
DE Includes:
DE RecName: Full=Methylphosphotriester-DNA--protein-cysteine S-methyltransferase;
DE EC=2.1.1.n11;
DE AltName: Full=Methylphosphotriester-DNA methyltransferase;
DE Includes:
DE RecName: Full=DNA-3-methyladenine glycosylase;
DE EC=3.2.2.21;
DE AltName: Full=DNA-3-methyladenine glycosidase;
GN Name=alkA; Synonyms=ada; OrderedLocusNames=MT1358;
OS Mycobacterium tuberculosis (strain CDC 1551 / Oshkosh).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83331;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=CDC 1551 / Oshkosh;
RX PubMed=12218036; DOI=10.1128/jb.184.19.5479-5490.2002;
RA Fleischmann R.D., Alland D., Eisen J.A., Carpenter L., White O.,
RA Peterson J.D., DeBoy R.T., Dodson R.J., Gwinn M.L., Haft D.H., Hickey E.K.,
RA Kolonay J.F., Nelson W.C., Umayam L.A., Ermolaeva M.D., Salzberg S.L.,
RA Delcher A., Utterback T.R., Weidman J.F., Khouri H.M., Gill J., Mikula A.,
RA Bishai W., Jacobs W.R. Jr., Venter J.C., Fraser C.M.;
RT "Whole-genome comparison of Mycobacterium tuberculosis clinical and
RT laboratory strains.";
RL J. Bacteriol. 184:5479-5490(2002).
CC -!- FUNCTION: Is involved in the adaptive response to alkylation damage in
CC DNA caused by alkylating agents. Repairs the Sp diastereomer of DNA
CC methylphosphotriester lesions by a direct and irreversible transfer of
CC the methyl group to one of its own cysteine residues. Also catalyzes
CC the hydrolysis of the deoxyribose N-glycosidic bond to excise 3-
CC methyladenine, 3-methylguanine, 7-methylguanine, O2-methylthymine, and
CC O2-methylcytosine from the damaged DNA polymer formed by alkylation
CC lesions (By similarity). {ECO:0000250}.
CC -!- FUNCTION: The methylation of Alka by methylphosphotriesters in DNA
CC leads to its activation as a transcriptional regulator that activates
CC the transcription of its own gene and other alkylation resistance
CC genes. {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2'-deoxyribonucleoside 5'-methylphosphotriester)-DNA + L-
CC cysteinyl-[protein] = 2'-deoxyribonucleotide-DNA + H(+) + S-methyl-L-
CC cysteinyl-[protein]; Xref=Rhea:RHEA:56324, Rhea:RHEA-COMP:10131,
CC Rhea:RHEA-COMP:10132, Rhea:RHEA-COMP:14462, Rhea:RHEA-COMP:14463,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29950, ChEBI:CHEBI:82612,
CC ChEBI:CHEBI:140284, ChEBI:CHEBI:140286; EC=2.1.1.n11;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Hydrolysis of alkylated DNA, releasing 3-methyladenine, 3-
CC methylguanine, 7-methylguanine and 7-methyladenine.; EC=3.2.2.21;
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC -!- MISCELLANEOUS: This enzyme catalyzes only one turnover and therefore is
CC not strictly catalytic. According to one definition, an enzyme is a
CC biocatalyst that acts repeatedly and over many reaction cycles.
CC -!- SIMILARITY: In the C-terminal section; belongs to the alkylbase DNA
CC glycosidase AlkA family. {ECO:0000305}.
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DR EMBL; AE000516; AAK45620.1; -; Genomic_DNA.
DR PIR; A70769; A70769.
DR RefSeq; WP_003900313.1; NZ_KK341227.1.
DR AlphaFoldDB; P9WJW2; -.
DR SMR; P9WJW2; -.
DR EnsemblBacteria; AAK45620; AAK45620; MT1358.
DR KEGG; mtc:MT1358; -.
DR PATRIC; fig|83331.31.peg.1464; -.
DR HOGENOM; CLU_000445_72_6_11; -.
DR Proteomes; UP000001020; Chromosome.
DR GO; GO:0008725; F:DNA-3-methyladenine glycosylase activity; IEA:UniProtKB-EC.
DR GO; GO:0052822; F:DNA-3-methylguanine glycosylase activity; IEA:UniProtKB-EC.
DR GO; GO:0052821; F:DNA-7-methyladenine glycosylase activity; IEA:UniProtKB-EC.
DR GO; GO:0043916; F:DNA-7-methylguanine glycosylase activity; IEA:UniProtKB-EC.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IEA:InterPro.
DR GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0043565; F:sequence-specific DNA binding; IEA:InterPro.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0006284; P:base-excision repair; IEA:InterPro.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR CDD; cd00056; ENDO3c; 1.
DR Gene3D; 1.10.1670.10; -; 1.
DR Gene3D; 3.30.310.20; -; 1.
DR Gene3D; 3.40.10.10; -; 1.
DR InterPro; IPR035451; Ada-like_dom_sf.
DR InterPro; IPR004026; Ada_DNA_repair_Zn-bd.
DR InterPro; IPR010316; AlkA_N.
DR InterPro; IPR037046; AlkA_N_sf.
DR InterPro; IPR011257; DNA_glycosylase.
DR InterPro; IPR003265; HhH-GPD_domain.
DR InterPro; IPR023170; HhH_base_excis_C.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR018060; HTH_AraC.
DR InterPro; IPR018062; HTH_AraC-typ_CS.
DR Pfam; PF02805; Ada_Zn_binding; 1.
DR Pfam; PF06029; AlkA_N; 1.
DR Pfam; PF00730; HhH-GPD; 1.
DR Pfam; PF12833; HTH_18; 1.
DR SMART; SM01009; AlkA_N; 1.
DR SMART; SM00478; ENDO3c; 1.
DR SMART; SM00342; HTH_ARAC; 1.
DR SUPFAM; SSF46689; SSF46689; 1.
DR SUPFAM; SSF48150; SSF48150; 1.
DR SUPFAM; SSF57884; SSF57884; 1.
DR PROSITE; PS00041; HTH_ARAC_FAMILY_1; 1.
DR PROSITE; PS01124; HTH_ARAC_FAMILY_2; 1.
PE 3: Inferred from homology;
KW Activator; DNA damage; DNA repair; DNA-binding; Hydrolase; Metal-binding;
KW Methyltransferase; Multifunctional enzyme; Transcription;
KW Transcription regulation; Transferase; Zinc.
FT CHAIN 1..496
FT /note="Probable bifunctional transcriptional activator/DNA
FT repair enzyme AlkA"
FT /id="PRO_0000427760"
FT DOMAIN 87..185
FT /note="HTH araC/xylS-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00593"
FT DNA_BIND 104..125
FT /note="H-T-H motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00593"
FT REGION 1..185
FT /note="Methylphosphotriester-DNA--protein-cysteine
FT methyltransferase"
FT REGION 202..354
FT /note="DNA-3-methyladenine glycosylase"
FT ACT_SITE 34
FT /note="Nucleophile; methyl group acceptor from
FT methylphosphotriester"
FT /evidence="ECO:0000250"
FT ACT_SITE 441
FT /note="Proton acceptor; for DNA glycosylase activity"
FT /evidence="ECO:0000250"
FT BINDING 30
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /evidence="ECO:0000250"
FT BINDING 34
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 38
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 41
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /evidence="ECO:0000250"
FT BINDING 63
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /evidence="ECO:0000250"
FT BINDING 65
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 68
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT SITE 421
FT /note="Determinant for substrate specificity and/or DNA
FT glycosylase activity"
FT /evidence="ECO:0000250"
SQ SEQUENCE 496 AA; 53743 MW; CA1F52032181268F CRC64;
MHDDFERCYR AIQSKDARFD GWFVVAVLTT GVYCRPSCPV RPPFARNVRF LPTAAAAQGE
GFRACKRCRP DASPGSPEWN VRSDVVARAM RLIADGTVDR DGVSGLAAQL GYTIRQLERL
LQAVVGAGPL ALARAQRMQT ARVLIETTNL PFGDVAFAAG FSSIRQFNDT VRLACDGTPT
ALRARAAARF ESATASAGTV SLRLPVRAPF AFEGVFGHLA ATAVPGCEEV RDGAYRRTLR
LPWGNGIVSL TPAPDHVRCL LVLDDFRDLM TATARCRRLL DLDADPEAIV EALGADPDLR
AVVGKAPGQR IPRTVDEAEF AVRAVLAQQV STKAASTHAG RLVAAYGRPV HDRHGALTHT
FPSIEQLAEI DPGHLAVPKA RQRTINALVA SLADKSLVLD AGCDWQRARG QLLALPGVGP
WTAEVIAMRG LGDPDAFPAS DLGLRLAAKK LGLPAQRRAL TVHSARWRPW RSYATQHLWT
TLEHPVNQWP PQEKIA
