IPDA_MYCTU
ID IPDA_MYCTU Reviewed; 292 AA.
AC P9WPW1; L0TCX1; P71850;
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=Cholesterol ring-cleaving hydrolase IpdA subunit {ECO:0000305};
DE EC=4.1.99.- {ECO:0000269|PubMed:29581275};
DE AltName: Full=(3E)-2-(2-carboxylatoethyl)-3-methyl-6-oxocyclohex-1-ene-1-carboxyl-CoA hydrolase alpha subunit {ECO:0000305};
DE Short=COCHEA-CoA hydrolase alpha subunit {ECO:0000305};
GN Name=ipdA {ECO:0000303|PubMed:28377529}; OrderedLocusNames=Rv3551;
GN ORFNames=MTCY03C7.05c;
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 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 [3]
RP FUNCTION, PATHWAY, AND DISRUPTION PHENOTYPE.
RC STRAIN=Erdman;
RX PubMed=28377529; DOI=10.1128/mbio.00321-17;
RA Crowe A.M., Casabon I., Brown K.L., Liu J., Lian J., Rogalski J.C.,
RA Hurst T.E., Snieckus V., Foster L.J., Eltis L.D.;
RT "Catabolism of the last two steroid rings in Mycobacterium tuberculosis and
RT other bacteria.";
RL MBio 8:e00321-e00321(2017).
RN [4] {ECO:0007744|PDB:6CON}
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) IN COMPLEX WITH IPDB, FUNCTION,
RP CATALYTIC ACTIVITY, AND SUBUNIT.
RX PubMed=29581275; DOI=10.1073/pnas.1717015115;
RA Crowe A.M., Workman S.D., Watanabe N., Worrall L.J., Strynadka N.C.J.,
RA Eltis L.D.;
RT "IpdAB, a virulence factor in Mycobacterium tuberculosis, is a cholesterol
RT ring-cleaving hydrolase.";
RL Proc. Natl. Acad. Sci. U.S.A. 115:E3378-E3387(2018).
CC -!- FUNCTION: Involved in the final steps of cholesterol and steroid
CC degradation (PubMed:28377529). Opens the last steroid ring of
CC cholesterol by catalyzing the hydrolysis of (3E)-2-(2-
CC carboxylatoethyl)-3-methyl-6-oxocyclohex-1-ene-1-carboxyl-CoA (COCHEA-
CC CoA) to 6-methyl-3,7-dioxodecanedioyl-CoA (MeDODA-CoA)
CC (PubMed:29581275). {ECO:0000269|PubMed:28377529,
CC ECO:0000269|PubMed:29581275}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3E)-2-(2-carboxylatoethyl)-3-methyl-6-oxocyclohex-1-ene-1-
CC carboxyl-CoA + H2O = 6-methyl-3,7-dioxodecanedioyl-CoA;
CC Xref=Rhea:RHEA:66364, ChEBI:CHEBI:15377, ChEBI:CHEBI:167101,
CC ChEBI:CHEBI:167102; Evidence={ECO:0000269|PubMed:29581275};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66365;
CC Evidence={ECO:0000269|PubMed:29581275};
CC -!- PATHWAY: Steroid metabolism; cholesterol degradation.
CC {ECO:0000269|PubMed:28377529}.
CC -!- SUBUNIT: Heterotetramer composed of 2 IpdA subunits and 2 IpdB
CC subunits. {ECO:0000269|PubMed:29581275}.
CC -!- DISRUPTION PHENOTYPE: IpdAB double deletion mutant does not grow on
CC cholesterol, but grows as the wild-type on glycerol. In the presence of
CC cholesterol, ipdAB double deletion mutant accumulates COCHEA-CoA.
CC Double mutant does not survive in macrophages and displays severely
CC depleted CoASH levels that correlate with a cholesterol-dependent
CC toxicity. {ECO:0000269|PubMed:28377529}.
CC -!- SIMILARITY: Belongs to the 3-oxoacid CoA-transferase subunit A family.
CC {ECO:0000305}.
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DR EMBL; AL123456; CCP46373.1; -; Genomic_DNA.
DR PIR; H70677; H70677.
DR RefSeq; NP_218068.1; NC_000962.3.
DR RefSeq; WP_003900094.1; NZ_NVQJ01000014.1.
DR PDB; 6CON; X-ray; 2.10 A; A/C/E/G=1-292.
DR PDBsum; 6CON; -.
DR AlphaFoldDB; P9WPW1; -.
DR SMR; P9WPW1; -.
DR STRING; 83332.Rv3551; -.
DR PaxDb; P9WPW1; -.
DR DNASU; 887235; -.
DR GeneID; 887235; -.
DR KEGG; mtu:Rv3551; -.
DR TubercuList; Rv3551; -.
DR eggNOG; COG1788; Bacteria.
DR OMA; YDPWFAK; -.
DR PhylomeDB; P9WPW1; -.
DR BioCyc; MetaCyc:G185E-7828-MON; -.
DR UniPathway; UPA01058; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0008410; F:CoA-transferase activity; IEA:InterPro.
DR GO; GO:0016829; F:lyase activity; IEA:UniProtKB-KW.
DR GO; GO:0051701; P:biological process involved in interaction with host; IMP:MTBBASE.
DR GO; GO:0006707; P:cholesterol catabolic process; IEA:UniProtKB-UniPathway.
DR InterPro; IPR004165; CoA_trans_fam_I.
DR InterPro; IPR037171; NagB/RpiA_transferase-like.
DR Pfam; PF01144; CoA_trans; 1.
DR SMART; SM00882; CoA_trans; 1.
DR SUPFAM; SSF100950; SSF100950; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cholesterol metabolism; Lipid metabolism; Lyase;
KW Reference proteome; Steroid metabolism; Sterol metabolism.
FT CHAIN 1..292
FT /note="Cholesterol ring-cleaving hydrolase IpdA subunit"
FT /id="PRO_0000157928"
FT HELIX 8..12
FT /evidence="ECO:0007829|PDB:6CON"
FT STRAND 20..23
FT /evidence="ECO:0007829|PDB:6CON"
FT HELIX 33..41
FT /evidence="ECO:0007829|PDB:6CON"
FT STRAND 46..54
FT /evidence="ECO:0007829|PDB:6CON"
FT HELIX 55..62
FT /evidence="ECO:0007829|PDB:6CON"
FT STRAND 66..74
FT /evidence="ECO:0007829|PDB:6CON"
FT HELIX 84..91
FT /evidence="ECO:0007829|PDB:6CON"
FT STRAND 95..99
FT /evidence="ECO:0007829|PDB:6CON"
FT HELIX 102..113
FT /evidence="ECO:0007829|PDB:6CON"
FT STRAND 117..122
FT /evidence="ECO:0007829|PDB:6CON"
FT TURN 123..126
FT /evidence="ECO:0007829|PDB:6CON"
FT HELIX 129..132
FT /evidence="ECO:0007829|PDB:6CON"
FT TURN 133..135
FT /evidence="ECO:0007829|PDB:6CON"
FT STRAND 139..141
FT /evidence="ECO:0007829|PDB:6CON"
FT STRAND 153..158
FT /evidence="ECO:0007829|PDB:6CON"
FT STRAND 162..172
FT /evidence="ECO:0007829|PDB:6CON"
FT HELIX 188..193
FT /evidence="ECO:0007829|PDB:6CON"
FT STRAND 195..205
FT /evidence="ECO:0007829|PDB:6CON"
FT HELIX 208..214
FT /evidence="ECO:0007829|PDB:6CON"
FT HELIX 217..219
FT /evidence="ECO:0007829|PDB:6CON"
FT HELIX 224..226
FT /evidence="ECO:0007829|PDB:6CON"
FT STRAND 228..232
FT /evidence="ECO:0007829|PDB:6CON"
FT TURN 234..239
FT /evidence="ECO:0007829|PDB:6CON"
FT HELIX 250..260
FT /evidence="ECO:0007829|PDB:6CON"
FT HELIX 263..273
FT /evidence="ECO:0007829|PDB:6CON"
FT STRAND 274..276
FT /evidence="ECO:0007829|PDB:6CON"
FT HELIX 278..291
FT /evidence="ECO:0007829|PDB:6CON"
SQ SEQUENCE 292 AA; 31723 MW; 5C841A83422E4D5D CRC64;
MPDKRTALDD AVAQLRSGMT IGIAGWGSRR KPMAFVRAIL RSDVTDLTVV TYGGPDLGLL
CSAGKVKRVY YGFVSLDSPP FYDPWFAHAR TSGAIEAREM DEGMLRCGLQ AAAQRLPFLP
IRAGLGSSVP QFWAGELQTV TSPYPAPGGG YETLIAMPAL RLDAAFAHLN LGDSHGNAAY
TGIDPYFDDL FLMAAERRFL SVERIVATEE LVKSVPPQAL LVNRMMVDAI VEAPGGAHFT
TAAPDYGRDE QFQRHYAEAA STQVGWQQFV HTYLSGTEAD YQAAVHNFGA SR
