MMAA2_MYCTU
ID MMAA2_MYCTU Reviewed; 287 AA.
AC Q79FX6; L0T7B6;
DT 05-OCT-2010, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 113.
DE RecName: Full=Cyclopropane mycolic acid synthase MmaA2;
DE Short=CMAS;
DE EC=2.1.1.79 {ECO:0000269|PubMed:12502719, ECO:0000269|PubMed:20472794};
DE AltName: Full=Cyclopropane-fatty-acyl-phospholipid synthase;
DE Short=CFA synthase;
DE AltName: Full=Mycolic acid methyltransferase;
DE Short=MA-MT;
DE AltName: Full=S-adenosylmethionine-dependent methyltransferase;
DE Short=AdoMet-MT;
DE Short=SAM-MT;
GN Name=mmaA2; Synonyms=mma2; OrderedLocusNames=Rv0644c;
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 THE BIOSYNTHESIS OF CYCLOPROPANE RING IN THE ALPHA MYCOLATE,
RP CATALYTIC ACTIVITY, PATHWAY, AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 35801 / TMC 107 / Erdman;
RX PubMed=12502719; DOI=10.1074/jbc.m212458200;
RA Glickman M.S.;
RT "The mmaA2 gene of Mycobacterium tuberculosis encodes the distal
RT cyclopropane synthase of the alpha-mycolic acid.";
RL J. Biol. Chem. 278:7844-7849(2003).
RN [3]
RP ACTIVITY REGULATION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=18094751; DOI=10.1371/journal.pone.0001343;
RA Alahari A., Trivelli X., Guerardel Y., Dover L.G., Besra G.S.,
RA Sacchettini J.C., Reynolds R.C., Coxon G.D., Kremer L.;
RT "Thiacetazone, an antitubercular drug that inhibits cyclopropanation of
RT cell wall mycolic acids in mycobacteria.";
RL PLoS ONE 2:E1343-E1343(2007).
RN [4]
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 [5]
RP ACTIVITY REGULATION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=19439410; DOI=10.1074/jbc.m809599200;
RA Vaubourgeix J., Bardou F., Boissier F., Julien S., Constant P., Ploux O.,
RA Daffe M., Quemard A., Mourey L.;
RT "S-adenosyl-N-decyl-aminoethyl, a potent bisubstrate inhibitor of
RT mycobacterium tuberculosis mycolic acid methyltransferases.";
RL J. Biol. Chem. 284:19321-19330(2009).
RN [6]
RP FUNCTION IN OXYGEN-CONTAINING MYCOLATES AND IN ALPHA-MYCOLATES
RP BIOSYNTHESIS, CATALYTIC ACTIVITY, PATHWAY, 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 [7]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT VAL-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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).
RN [8] {ECO:0007744|PDB:1TPY}
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) IN COMPLEX WITH
RP S-ADENOSYL-L-HOMOCYSTEINE.
RC STRAIN=ATCC 25618 / H37Rv;
RA Smith C.V., Sacchettini J.C.;
RT "Structure of the cyclopropane synthase mmaA2 from Mycobacterium
RT tuberculosis.";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Catalyzes the conversion of a double bond to a cis
CC cyclopropane ring at the distal position of an alpha mycolic acid via
CC the transfer of a methylene group from S-adenosyl-L-methionine. MmaA2
CC also catalyzes the biosynthesis of the cis-cyclopropanated
CC methoxymycolates. Cyclopropanated mycolic acids are key factors
CC participating in cell envelope permeability, host immunomodulation and
CC persistence. {ECO:0000269|PubMed:12502719,
CC ECO:0000269|PubMed:20472794}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-acyl-2-(9Z)-enoyl-sn-glycero-3-phospholipid + S-adenosyl-L-
CC methionine = 1-acyl-2-(9-cyclopronane)-acyl-sn-glycero-3-phospholipid
CC + H(+) + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:11988,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:76593, ChEBI:CHEBI:76594; EC=2.1.1.79;
CC Evidence={ECO:0000269|PubMed:12502719, ECO:0000269|PubMed:20472794};
CC -!- ACTIVITY REGULATION: Inhibited by S-adenosyl-N-decyl-aminoethyl (SADAE)
CC and thiacetazone (TAC). {ECO:0000269|PubMed:18094751,
CC ECO:0000269|PubMed:19439410}.
CC -!- PATHWAY: Lipid metabolism; mycolic acid biosynthesis.
CC {ECO:0000305|PubMed:12502719, ECO:0000305|PubMed:20472794}.
CC -!- DISRUPTION PHENOTYPE: Disruption of this gene suppresses a cyclopropane
CC group at the distal position of alpha mycolic acid. Mutant produces
CC fully cyclopropanated methoxymycolates, but the efficiency of cis-
CC methoxymycolate cyclopropanation is reduced, leading to accumulation of
CC unsaturated methoxymycolate derivatives. Cis/trans ratios in purified
CC ketomycolates are unchanged (PubMed:12502719). Cells lacking both cmaA2
CC and mmaA2 genes cannot cis cyclopropanate methoxymycolates or
CC ketomycolates (PubMed:20472794). {ECO:0000269|PubMed:12502719,
CC ECO:0000269|PubMed:20472794}.
CC -!- SIMILARITY: Belongs to the CFA/CMAS family. {ECO:0000305}.
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DR EMBL; AL123456; CCP43387.1; -; Genomic_DNA.
DR RefSeq; NP_215158.1; NC_000962.3.
DR RefSeq; WP_003900985.1; NZ_NVQJ01000007.1.
DR PDB; 1TPY; X-ray; 2.20 A; A=1-287.
DR PDBsum; 1TPY; -.
DR AlphaFoldDB; Q79FX6; -.
DR SMR; Q79FX6; -.
DR STRING; 83332.Rv0644c; -.
DR DrugBank; DB01718; Cetrimonium.
DR DrugBank; DB01752; S-adenosyl-L-homocysteine.
DR iPTMnet; Q79FX6; -.
DR PaxDb; Q79FX6; -.
DR DNASU; 888061; -.
DR GeneID; 45424604; -.
DR GeneID; 888061; -.
DR KEGG; mtu:Rv0644c; -.
DR TubercuList; Rv0644c; -.
DR eggNOG; COG2230; Bacteria.
DR InParanoid; Q79FX6; -.
DR OMA; LHCITAQ; -.
DR PhylomeDB; Q79FX6; -.
DR BioCyc; MetaCyc:G185E-4787-MON; -.
DR UniPathway; UPA00915; -.
DR EvolutionaryTrace; Q79FX6; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0008825; F:cyclopropane-fatty-acyl-phospholipid synthase activity; IMP:UniProtKB.
DR GO; GO:0008168; F:methyltransferase activity; 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 3D-structure; Acetylation; Lipid biosynthesis; Lipid metabolism;
KW Methyltransferase; Reference proteome; S-adenosyl-L-methionine;
KW Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:21969609"
FT CHAIN 2..287
FT /note="Cyclopropane mycolic acid synthase MmaA2"
FT /id="PRO_0000398359"
FT ACT_SITE 269
FT /evidence="ECO:0000250"
FT BINDING 33..34
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|Ref.8"
FT BINDING 72..74
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|Ref.8"
FT BINDING 94..99
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|Ref.8"
FT BINDING 123..124
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|Ref.8"
FT BINDING 136
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|Ref.8"
FT MOD_RES 2
FT /note="N-acetylvaline"
FT /evidence="ECO:0007744|PubMed:21969609"
FT HELIX 9..16
FT /evidence="ECO:0007829|PDB:1TPY"
FT HELIX 20..24
FT /evidence="ECO:0007829|PDB:1TPY"
FT HELIX 45..57
FT /evidence="ECO:0007829|PDB:1TPY"
FT TURN 58..61
FT /evidence="ECO:0007829|PDB:1TPY"
FT STRAND 67..72
FT /evidence="ECO:0007829|PDB:1TPY"
FT HELIX 77..86
FT /evidence="ECO:0007829|PDB:1TPY"
FT STRAND 89..95
FT /evidence="ECO:0007829|PDB:1TPY"
FT HELIX 97..108
FT /evidence="ECO:0007829|PDB:1TPY"
FT STRAND 116..121
FT /evidence="ECO:0007829|PDB:1TPY"
FT HELIX 123..125
FT /evidence="ECO:0007829|PDB:1TPY"
FT STRAND 131..137
FT /evidence="ECO:0007829|PDB:1TPY"
FT HELIX 139..142
FT /evidence="ECO:0007829|PDB:1TPY"
FT HELIX 144..146
FT /evidence="ECO:0007829|PDB:1TPY"
FT HELIX 147..157
FT /evidence="ECO:0007829|PDB:1TPY"
FT STRAND 163..171
FT /evidence="ECO:0007829|PDB:1TPY"
FT HELIX 174..179
FT /evidence="ECO:0007829|PDB:1TPY"
FT HELIX 186..198
FT /evidence="ECO:0007829|PDB:1TPY"
FT HELIX 208..218
FT /evidence="ECO:0007829|PDB:1TPY"
FT STRAND 221..227
FT /evidence="ECO:0007829|PDB:1TPY"
FT HELIX 229..245
FT /evidence="ECO:0007829|PDB:1TPY"
FT HELIX 247..253
FT /evidence="ECO:0007829|PDB:1TPY"
FT HELIX 256..275
FT /evidence="ECO:0007829|PDB:1TPY"
FT STRAND 277..286
FT /evidence="ECO:0007829|PDB:1TPY"
SQ SEQUENCE 287 AA; 32724 MW; 669C3224C6B178C0 CRC64;
MVNDLTPHFE DVQAHYDLSD DFFRLFLDPT QTYSCAHFER EDMTLEEAQI AKIDLALGKL
GLQPGMTLLD IGCGWGATMR RAIAQYDVNV VGLTLSKNQA AHVQKSFDEM DTPRDRRVLL
AGWEQFNEPV DRIVSIGAFE HFGHDRHADF FARAHKILPP DGVLLLHTIT GLTRQQMVDH
GLPLTLWLAR FLKFIATEIF PGGQPPTIEM VEEQSAKTGF TLTRRQSLQP HYARTLDLWA
EALQEHKSEA IAIQSEEVYE RYMKYLTGCA KLFRVGYIDV NQFTLAK
