PRPC_MYCTU
ID PRPC_MYCTU Reviewed; 393 AA.
AC I6Y9Q3;
DT 29-APR-2015, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2012, sequence version 1.
DT 03-AUG-2022, entry version 59.
DE RecName: Full=2-methylcitrate synthase {ECO:0000303|PubMed:18375549};
DE Short=2-MCS {ECO:0000303|PubMed:18375549};
DE Short=MCS {ECO:0000303|PubMed:18375549};
DE EC=2.3.3.5 {ECO:0000250|UniProtKB:H8F0D7};
DE AltName: Full=Citrate synthase {ECO:0000303|PubMed:18375549};
DE EC=2.3.3.16 {ECO:0000250|UniProtKB:H8F0D7};
GN Name=prpC; OrderedLocusNames=Rv1131, RVBD_1131; ORFNames=P425_01180;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RG The Broad Institute Genome Sequencing Platform;
RA Galagan J., Kreiswirth B., Dobos K., Fortune S., Fitzgerald M., Young S.K.,
RA Zeng Q., Gargeya S., Abouelleil A., Alvarado L., Berlin A.M., Chapman S.B.,
RA Gainer-Dewar J., Goldberg J., Gnerre S., Griggs A., Gujja S., Hansen M.,
RA Howarth C., Imamovic A., Larimer J., McCowan C., Murphy C., Pearson M.,
RA Poon T., Priest M., Roberts A., Saif S., Shea T., Sykes S., Wortman J.,
RA Nusbaum C., Birren B.;
RT "The genome sequence of Mycobacterium tuberculosis H37Rv.";
RL Submitted (NOV-2013) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=H37Rv;
RG The Broad Institute Genomics Platform;
RG The Broad Institute Genome Sequencing Center for Infectious Disease;
RA Earl A.M., Kreiswirth B., Gomez J., Victor T., Desjardins C., Abeel T.,
RA Young S., Zeng Q., Gargeya S., Abouelleil A., Alvarado L., Chapman S.B.,
RA Gainer-Dewar J., Goldberg J., Griggs A., Gujja S., Hansen M., Howarth C.,
RA Imamovic A., Larimer J., Murphy C., Naylor J., Pearson M., Poon T.W.,
RA Priest M., Roberts A., Saif S., Shea T., Sykes S., Wortman J., Nusbaum C.,
RA Birren B.;
RT "The genome sequence of Mycobacterium tuberculosis H37Rv.";
RL Submitted (APR-2014) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP FUNCTION, DISRUPTION PHENOTYPE, AND SUBSTRATE SPECIFICITY.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=18375549; DOI=10.1128/jb.01767-07;
RA Savvi S., Warner D.F., Kana B.D., McKinney J.D., Mizrahi V., Dawes S.S.;
RT "Functional characterization of a vitamin B12-dependent methylmalonyl
RT pathway in Mycobacterium tuberculosis: implications for propionate
RT metabolism during growth on fatty acids.";
RL J. Bacteriol. 190:3886-3895(2008).
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).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=H37Rv;
RX PubMed=22365605; DOI=10.1016/j.chembiol.2011.12.016;
RA Griffin J.E., Pandey A.K., Gilmore S.A., Mizrahi V., McKinney J.D.,
RA Bertozzi C.R., Sassetti C.M.;
RT "Cholesterol catabolism by Mycobacterium tuberculosis requires
RT transcriptional and metabolic adaptations.";
RL Chem. Biol. 19:218-227(2012).
RN [7]
RP INDUCTION.
RC STRAIN=H37Rv;
RX PubMed=22916289; DOI=10.1371/journal.pone.0043651;
RA Masiewicz P., Brzostek A., Wolanski M., Dziadek J.,
RA Zakrzewska-Czerwinska J.;
RT "A novel role of the PrpR as a transcription factor involved in the
RT regulation of methylcitrate pathway in Mycobacterium tuberculosis.";
RL PLoS ONE 7:E43651-E43651(2012).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) IN COMPLEX WITH SUBSTRATE ANALOG,
RP AND SUBUNIT.
RC STRAIN=H37Rv;
RG Seattle Structural Genomics Center for Infectious Disease (SSGCID);
RA Edwards T.E., Staker B.L.;
RT "Crystal structure of methylcitrate synthase from Mycobacterium
RT tuberculosis.";
RL Submitted (JUN-2009) to the PDB data bank.
CC -!- FUNCTION: Involved in the catabolism of short chain fatty acids (SCFA)
CC via the tricarboxylic acid (TCA)(acetyl degradation route) and via the
CC 2-methylcitrate cycle I (propionate degradation route). Catalyzes the
CC Claisen condensation of propionyl-CoA and oxaloacetate (OAA) to yield
CC 2-methylcitrate (2-MC) and CoA. Also catalyzes the condensation of
CC oxaloacetate with acetyl-CoA. {ECO:0000269|PubMed:18375549,
CC ECO:0000269|PubMed:22365605}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + oxaloacetate + propanoyl-CoA = (2S,3S)-2-methylcitrate +
CC CoA + H(+); Xref=Rhea:RHEA:23780, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16452, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57392, ChEBI:CHEBI:58853; EC=2.3.3.5;
CC Evidence={ECO:0000250|UniProtKB:H8F0D7};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-CoA + H2O + oxaloacetate = citrate + CoA + H(+);
CC Xref=Rhea:RHEA:16845, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16452, ChEBI:CHEBI:16947, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57288; EC=2.3.3.16;
CC Evidence={ECO:0000250|UniProtKB:H8F0D7};
CC -!- PATHWAY: Organic acid metabolism; propanoate degradation.
CC {ECO:0000305|PubMed:18375549}.
CC -!- PATHWAY: Carbohydrate metabolism; tricarboxylic acid cycle; isocitrate
CC from oxaloacetate: step 1/2. {ECO:0000305|PubMed:18375549}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|Ref.8}.
CC -!- INDUCTION: Activated by PrpR. {ECO:0000269|PubMed:22916289}.
CC -!- DISRUPTION PHENOTYPE: Cells lacking both prpC and prpD genes are unable
CC to grow on propionate or cholesterol as the sole carbon source.
CC {ECO:0000269|PubMed:18375549, ECO:0000269|PubMed:22365605}.
CC -!- MISCELLANEOUS: The vitamin B12 restores growth of the prpDC mutant. It
CC suggests the capacity of the MCM-dependent methylmalonyl pathway to
CC support the metabolism of propionate independently of the methylcitrate
CC cycle. {ECO:0000269|PubMed:18375549}.
CC -!- SIMILARITY: Belongs to the citrate synthase family. {ECO:0000305}.
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DR EMBL; AL123456; CCP43885.1; -; Genomic_DNA.
DR EMBL; CP003248; AFN49030.1; -; Genomic_DNA.
DR EMBL; JLDD01000012; KBJ36377.1; -; Genomic_DNA.
DR RefSeq; NP_215647.1; NC_000962.3.
DR RefSeq; WP_003405909.1; NZ_NVQJ01000021.1.
DR PDB; 3HWK; X-ray; 2.30 A; A/B/C/D/E/F/G/H=1-393.
DR PDBsum; 3HWK; -.
DR AlphaFoldDB; I6Y9Q3; -.
DR SMR; I6Y9Q3; -.
DR STRING; 83332.Rv1131; -.
DR PaxDb; I6Y9Q3; -.
DR PRIDE; I6Y9Q3; -.
DR DNASU; 888949; -.
DR GeneID; 45425104; -.
DR GeneID; 888949; -.
DR KEGG; mtu:Rv1131; -.
DR KEGG; mtv:RVBD_1131; -.
DR PATRIC; fig|83332.111.peg.1263; -.
DR TubercuList; Rv1131; -.
DR eggNOG; COG0372; Bacteria.
DR OMA; NEAVMHM; -.
DR PhylomeDB; I6Y9Q3; -.
DR UniPathway; UPA00223; UER00717.
DR UniPathway; UPA00946; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IEA:InterPro.
DR GO; GO:0050440; F:2-methylcitrate synthase activity; ISS:UniProtKB.
DR GO; GO:0004108; F:citrate (Si)-synthase activity; IBA:GO_Central.
DR GO; GO:0036440; F:citrate synthase activity; ISS:UniProtKB.
DR GO; GO:0005975; P:carbohydrate metabolic process; IBA:GO_Central.
DR GO; GO:0019679; P:propionate metabolic process, methylcitrate cycle; IMP:UniProtKB.
DR GO; GO:0006099; P:tricarboxylic acid cycle; IBA:GO_Central.
DR Gene3D; 1.10.230.10; -; 1.
DR Gene3D; 1.10.580.10; -; 1.
DR InterPro; IPR011278; 2-MeCitrate/Citrate_synth_II.
DR InterPro; IPR016142; Citrate_synth-like_lrg_a-sub.
DR InterPro; IPR016143; Citrate_synth-like_sm_a-sub.
DR InterPro; IPR002020; Citrate_synthase.
DR InterPro; IPR019810; Citrate_synthase_AS.
DR InterPro; IPR024176; Citrate_synthase_bac-typ.
DR InterPro; IPR036969; Citrate_synthase_sf.
DR PANTHER; PTHR11739; PTHR11739; 1.
DR Pfam; PF00285; Citrate_synt; 1.
DR PIRSF; PIRSF001369; Citrate_synth; 1.
DR PRINTS; PR00143; CITRTSNTHASE.
DR SUPFAM; SSF48256; SSF48256; 1.
DR TIGRFAMs; TIGR01800; cit_synth_II; 1.
DR PROSITE; PS00480; CITRATE_SYNTHASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Reference proteome; Transferase; Tricarboxylic acid cycle.
FT CHAIN 1..393
FT /note="2-methylcitrate synthase"
FT /id="PRO_0000432969"
FT ACT_SITE 242
FT /evidence="ECO:0000250|UniProtKB:O34002"
FT ACT_SITE 281
FT /evidence="ECO:0000269|Ref.8"
FT ACT_SITE 332
FT /evidence="ECO:0000250|UniProtKB:O34002"
FT BINDING 92
FT /ligand="substrate"
FT /evidence="ECO:0000269|Ref.8"
FT BINDING 207
FT /ligand="substrate"
FT /evidence="ECO:0000269|Ref.8"
FT BINDING 275..279
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:O34002"
FT BINDING 290
FT /ligand="substrate"
FT /evidence="ECO:0000269|Ref.8"
FT BINDING 357
FT /ligand="substrate"
FT /evidence="ECO:0000269|Ref.8"
FT BINDING 376
FT /ligand="substrate"
FT /evidence="ECO:0000269|Ref.8"
FT HELIX 30..32
FT /evidence="ECO:0007829|PDB:3HWK"
FT STRAND 36..46
FT /evidence="ECO:0007829|PDB:3HWK"
FT TURN 47..50
FT /evidence="ECO:0007829|PDB:3HWK"
FT STRAND 51..54
FT /evidence="ECO:0007829|PDB:3HWK"
FT HELIX 59..65
FT /evidence="ECO:0007829|PDB:3HWK"
FT HELIX 68..77
FT /evidence="ECO:0007829|PDB:3HWK"
FT HELIX 83..95
FT /evidence="ECO:0007829|PDB:3HWK"
FT HELIX 101..109
FT /evidence="ECO:0007829|PDB:3HWK"
FT HELIX 116..129
FT /evidence="ECO:0007829|PDB:3HWK"
FT TURN 132..135
FT /evidence="ECO:0007829|PDB:3HWK"
FT HELIX 137..139
FT /evidence="ECO:0007829|PDB:3HWK"
FT HELIX 140..162
FT /evidence="ECO:0007829|PDB:3HWK"
FT HELIX 176..185
FT /evidence="ECO:0007829|PDB:3HWK"
FT HELIX 191..203
FT /evidence="ECO:0007829|PDB:3HWK"
FT HELIX 211..220
FT /evidence="ECO:0007829|PDB:3HWK"
FT TURN 221..223
FT /evidence="ECO:0007829|PDB:3HWK"
FT HELIX 226..237
FT /evidence="ECO:0007829|PDB:3HWK"
FT TURN 240..244
FT /evidence="ECO:0007829|PDB:3HWK"
FT HELIX 245..256
FT /evidence="ECO:0007829|PDB:3HWK"
FT HELIX 259..261
FT /evidence="ECO:0007829|PDB:3HWK"
FT HELIX 262..271
FT /evidence="ECO:0007829|PDB:3HWK"
FT HELIX 291..304
FT /evidence="ECO:0007829|PDB:3HWK"
FT HELIX 308..325
FT /evidence="ECO:0007829|PDB:3HWK"
FT HELIX 332..342
FT /evidence="ECO:0007829|PDB:3HWK"
FT HELIX 346..348
FT /evidence="ECO:0007829|PDB:3HWK"
FT HELIX 349..370
FT /evidence="ECO:0007829|PDB:3HWK"
FT STRAND 378..381
FT /evidence="ECO:0007829|PDB:3HWK"
SQ SEQUENCE 393 AA; 42969 MW; 5591E9F482CF1232 CRC64;
MTGPLAAARS VAATKSMTAP TVDERPDIKK GLAGVVVDTT AISKVVPQTN SLTYRGYPVQ
DLAARCSFEQ VAFLLWRGEL PTDAELALFS QRERASRRVD RSMLSLLAKL PDNCHPMDVV
RTAISYLGAE DPDEDDAAAN RAKAMRMMAV LPTIVAIDMR RRRGLPPIAP HSGLGYAQNF
LHMCFGEVPE TAVVSAFEQS MILYAEHGFN ASTFAARVVT STQSDIYSAV TGAIGALKGR
LHGGANEAVM HDMIEIGDPA NAREWLRAKL ARKEKIMGFG HRVYRHGDSR VPTMKRALER
VGTVRDGQRW LDIYQVLAAE MASATGILPN LDFPTGPAYY LMGFDIASFT PIFVMSRITG
WTAHIMEQAT ANALIRPLSA YCGHEQRVLP GTF
