MMAA1_MYCTU
ID MMAA1_MYCTU Reviewed; 286 AA.
AC P9WPB1; L0T754; P0A5Q0; P0C5C3; P72025; P94922; P96934;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 39.
DE RecName: Full=Mycolic acid methyltransferase MmaA1;
DE EC=2.1.1.-;
DE AltName: Full=S-adenosylmethionine-dependent methyltransferase;
DE Short=AdoMet-MT;
DE Short=SAM-MT;
GN Name=mmaA1; Synonyms=mma1; OrderedLocusNames=Rv0645c;
GN ORFNames=MTCY20H10.26c;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9634230; DOI=10.1038/31159;
RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT genome sequence.";
RL Nature 393:537-544(1998).
RN [2]
RP FUNCTION IN TRANS CYCLOPROPANE RING BIOSYNTHESIS.
RX PubMed=9092547; DOI=10.1074/jbc.272.15.10041;
RA Yuan Y., Crane D.C., Musser J.M., Sreevatsan S., Barry C.E. III;
RT "MMAS-1, the branch point between cis- and trans-cyclopropane-containing
RT oxygenated mycolates in Mycobacterium tuberculosis.";
RL J. Biol. Chem. 272:10041-10049(1997).
RN [3]
RP IDENTIFICATION AS A DRUG TARGET [LARGE SCALE ANALYSIS].
RX PubMed=19099550; DOI=10.1186/1752-0509-2-109;
RA Raman K., Yeturu K., Chandra N.;
RT "targetTB: a target identification pipeline for Mycobacterium tuberculosis
RT through an interactome, reactome and genome-scale structural analysis.";
RL BMC Syst. Biol. 2:109-109(2008).
RN [4]
RP FUNCTION IN TRANS CYCLOPROPANE RING BIOSYNTHESIS, AND DISRUPTION PHENOTYPE.
RX PubMed=20472794; DOI=10.1128/jb.00312-10;
RA Barkan D., Rao V., Sukenick G.D., Glickman M.S.;
RT "Redundant function of cmaA2 and mmaA2 in Mycobacterium tuberculosis cis
RT cyclopropanation of oxygenated mycolates.";
RL J. Bacteriol. 192:3661-3668(2010).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT mass spectrometry.";
RL Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
CC -!- FUNCTION: Involved in the conversion of a cis-olefin into a trans-
CC olefin with concomitant introduction of an allylic methyl branch at the
CC proximal position of the precursor to both the methoxy and ketomycolic
CC acids. It directly affects the cis- to trans ratio and indirectly
CC affects the keto to methoxy ratio. {ECO:0000269|PubMed:20472794,
CC ECO:0000269|PubMed:9092547}.
CC -!- PATHWAY: Lipid metabolism; mycolic acid biosynthesis.
CC -!- DISRUPTION PHENOTYPE: Disruption of this gene suppresses trans
CC cyclopropanated mycolate without accumulation of trans-unsaturated
CC oxygenated mycolates and shows an increased ability to form cords, thus
CC establishing MmaA1 as a negative regulator of cording in
CC M.tuberculosis. {ECO:0000269|PubMed:20472794}.
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC -!- SIMILARITY: Belongs to the CFA/CMAS family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AL123456; CCP43388.1; -; Genomic_DNA.
DR PIR; B70614; B70614.
DR RefSeq; NP_215159.1; NC_000962.3.
DR RefSeq; WP_003403310.1; NZ_NVQJ01000007.1.
DR AlphaFoldDB; P9WPB1; -.
DR SMR; P9WPB1; -.
DR STRING; 83332.Rv0645c; -.
DR PaxDb; P9WPB1; -.
DR DNASU; 888060; -.
DR GeneID; 45424605; -.
DR GeneID; 888060; -.
DR KEGG; mtu:Rv0645c; -.
DR TubercuList; Rv0645c; -.
DR eggNOG; COG2230; Bacteria.
DR OMA; AFKKERW; -.
DR PhylomeDB; P9WPB1; -.
DR UniPathway; UPA00915; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0016859; F:cis-trans isomerase activity; IDA:MTBBASE.
DR GO; GO:0008168; F:methyltransferase activity; IMP:UniProtKB.
DR GO; GO:0008610; P:lipid biosynthetic process; IMP:UniProtKB.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0071768; P:mycolic acid biosynthetic process; IDA:MTBBASE.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR003333; Mycolic_cyclopropane_synthase.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR PIRSF; PIRSF003085; CMAS; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
PE 1: Evidence at protein level;
KW Lipid biosynthesis; Lipid metabolism; Methyltransferase;
KW Reference proteome; S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..286
FT /note="Mycolic acid methyltransferase MmaA1"
FT /id="PRO_0000096504"
FT ACT_SITE 268
FT /evidence="ECO:0000250"
FT BINDING 32..33
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT BINDING 71..73
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT BINDING 93..98
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT BINDING 122..123
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
SQ SEQUENCE 286 AA; 33149 MW; 229EB252DCA8C552 CRC64;
MAKLRPYYEE SQSAYDISDD FFALFLDPTW VYTCAYFERD DMTLEEAQLA KVDLALDKLN
LEPGMTLLDV GCGWGGALVR AVEKYDVNVI GLTLSRNHYE RSKDRLAAIG TQRRAEARLQ
GWEEFEENVD RIVSFEAFDA FKKERYLTFF ERSYDILPDD GRMLLHSLFT YDRRWLHEQG
IALTMSDLRF LKFLRESIFP GGELPSEPDI VDNAQAAGFT IEHVQLLQQH YARTLDAWAA
NLQAARERAI AVQSEEVYNN FMHYLTGCAE RFRRGLINVA QFTMTK
