PRPD_MYCTU
ID PRPD_MYCTU Reviewed; 526 AA.
AC O06582; F2GGE2; I6XAP9; Q7D8S9;
DT 29-APR-2015, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=2-methylcitrate dehydratase {ECO:0000303|PubMed:18375549};
DE Short=2-MC dehydratase {ECO:0000303|PubMed:18375549};
DE EC=4.2.1.79 {ECO:0000250|UniProtKB:H8F0D6};
DE AltName: Full=Aconitate hydratase {ECO:0000250|UniProtKB:P77243};
DE Short=ACN {ECO:0000250|UniProtKB:P77243};
DE Short=Aconitase {ECO:0000250|UniProtKB:P77243};
DE EC=4.2.1.3 {ECO:0000250|UniProtKB:P77243};
GN Name=prpD; OrderedLocusNames=Rv1130, RVBD_1130; ORFNames=P425_01179;
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=ATCC 25618 / 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 PATHWAY.
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).
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 dehydration of 2-methylcitrate (2-MC) to yield the cis isomer of 2-
CC methyl-aconitate (PubMed:18375549, PubMed:22365605). Could also
CC catalyze the dehydration of citrate and the hydration of cis-aconitate
CC (By similarity). {ECO:0000250|UniProtKB:P77243,
CC ECO:0000269|PubMed:18375549, ECO:0000269|PubMed:22365605}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2S,3S)-2-methylcitrate = 2-methyl-cis-aconitate + H2O;
CC Xref=Rhea:RHEA:17725, ChEBI:CHEBI:15377, ChEBI:CHEBI:57872,
CC ChEBI:CHEBI:58853; EC=4.2.1.79;
CC Evidence={ECO:0000250|UniProtKB:H8F0D6};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=citrate = D-threo-isocitrate; Xref=Rhea:RHEA:10336,
CC ChEBI:CHEBI:15562, ChEBI:CHEBI:16947; EC=4.2.1.3;
CC Evidence={ECO:0000250|UniProtKB:P77243};
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}.
CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:P77243}.
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 on
CC propionate as the sole carbon source. It suggests the capacity of the
CC MCM-dependent methylmalonyl pathway to support the metabolism of
CC propionate independently of the methylcitrate cycle.
CC {ECO:0000269|PubMed:18375549}.
CC -!- SIMILARITY: Belongs to the PrpD family. {ECO:0000305}.
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DR EMBL; CP003248; AFN49029.1; -; Genomic_DNA.
DR EMBL; AL123456; CCP43884.1; -; Genomic_DNA.
DR EMBL; JLDD01000012; KBJ36376.1; -; Genomic_DNA.
DR RefSeq; NP_215646.1; NC_000962.3.
DR RefSeq; WP_003898738.1; NC_000962.3.
DR AlphaFoldDB; O06582; -.
DR SMR; O06582; -.
DR STRING; 83332.Rv1130; -.
DR PaxDb; O06582; -.
DR PRIDE; O06582; -.
DR DNASU; 885843; -.
DR GeneID; 885843; -.
DR KEGG; mtu:Rv1130; -.
DR KEGG; mtv:RVBD_1130; -.
DR PATRIC; fig|83332.111.peg.1262; -.
DR TubercuList; Rv1130; -.
DR eggNOG; COG2079; Bacteria.
DR OMA; ECTKHLG; -.
DR PhylomeDB; O06582; -.
DR UniPathway; UPA00223; UER00717.
DR UniPathway; UPA00946; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; HDA:MTBBASE.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR GO; GO:0047547; F:2-methylcitrate dehydratase activity; ISS:UniProtKB.
DR GO; GO:0003994; F:aconitate hydratase activity; IEA:UniProtKB-EC.
DR GO; GO:0047780; F:citrate dehydratase activity; IEA:UniProtKB-EC.
DR GO; GO:0008203; P:cholesterol metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0019629; P:propionate catabolic process, 2-methylcitrate cycle; IMP:MTBBASE.
DR GO; GO:0010447; P:response to acidic pH; IEP:MTBBASE.
DR GO; GO:0006099; P:tricarboxylic acid cycle; IEA:UniProtKB-UniPathway.
DR Gene3D; 1.10.4100.10; -; 1.
DR Gene3D; 3.30.1330.120; -; 1.
DR InterPro; IPR036148; MmgE/PrpD_sf.
DR InterPro; IPR042183; MmgE/PrpD_sf_1.
DR InterPro; IPR042188; MmgE/PrpD_sf_2.
DR InterPro; IPR005656; MmgE_PrpD.
DR InterPro; IPR045337; MmgE_PrpD_C.
DR InterPro; IPR045336; MmgE_PrpD_N.
DR PANTHER; PTHR16943; PTHR16943; 1.
DR Pfam; PF03972; MmgE_PrpD; 1.
DR Pfam; PF19305; MmgE_PrpD_C; 1.
DR SUPFAM; SSF103378; SSF103378; 1.
PE 1: Evidence at protein level;
KW Cholesterol metabolism; Lipid metabolism; Lyase; Reference proteome;
KW Steroid metabolism; Sterol metabolism; Tricarboxylic acid cycle.
FT CHAIN 1..526
FT /note="2-methylcitrate dehydratase"
FT /id="PRO_0000432935"
SQ SEQUENCE 526 AA; 57783 MW; C9D75AFA6CE6FAF3 CRC64;
MPDQDTKVRF FRVFCWCPVL RMVRIMLMHA VRAWRSADDF PCTEHMAYKI AQVAADPVDV
DPEVADMVCN RIIDNAAVSA ASMVRRPVTV ARHQALAHPV RHGAKVFGVE GSYSADWAAW
ANGVAARELD FHDTFLAADY SHPADNIPPL VAVAQQLGVC GAELIRGLVT AYEIHIDLTR
GICLHEHKID HVAHLGPAVA AGIGTMLRLD QETIYHAIGQ ALHLTTSTRQ SRKGAISSWK
AFAPAHAGKV GIEAVDRAMR GEGSPAPIWE GEDGVIAWLL AGPEHTYRVP LPAPGEPKRA
ILDSYTKQHS AEYQSQAPID LACRLRERIG DLDQIASIVL HTSHHTHVVI GTGSGDPQKF
DPDASRETLD HSLPYIFAVA LQDGCWHHER SYAPERARRS DTVALWHKIS TVEDPEWTRR
YHCADPAKKA FGARAEVTLH SGEVIVDELA VADAHPLGTR PFERKQYVEK FTELADGVVE
PVEQQRFLAV VESLADLESG AVGGLNVLVD PRVLDKAPVI PPGIFR