IPDB_MYCTU
ID IPDB_MYCTU Reviewed; 250 AA.
AC P9WPV9; L0TD49; P63652; P71848;
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 IpdB 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 beta subunit {ECO:0000305};
DE Short=COCHEA-CoA hydrolase beta subunit {ECO:0000305};
GN Name=ipdB {ECO:0000303|PubMed:28377529}; OrderedLocusNames=Rv3552;
GN ORFNames=MTCY03C7.03c;
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 IPDA, 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 B family.
CC {ECO:0000305}.
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DR EMBL; AL123456; CCP46374.1; -; Genomic_DNA.
DR PIR; A70678; A70678.
DR RefSeq; NP_218069.1; NC_000962.3.
DR RefSeq; WP_003419321.1; NZ_NVQJ01000014.1.
DR PDB; 6CON; X-ray; 2.10 A; B/D/F/H=1-250.
DR PDBsum; 6CON; -.
DR AlphaFoldDB; P9WPV9; -.
DR SMR; P9WPV9; -.
DR STRING; 83332.Rv3552; -.
DR PaxDb; P9WPV9; -.
DR DNASU; 887453; -.
DR GeneID; 45427536; -.
DR GeneID; 887453; -.
DR KEGG; mtu:Rv3552; -.
DR TubercuList; Rv3552; -.
DR eggNOG; COG2057; Bacteria.
DR OMA; YWVGNHS; -.
DR PhylomeDB; P9WPV9; -.
DR BioCyc; MetaCyc:G185E-7829-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 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..250
FT /note="Cholesterol ring-cleaving hydrolase IpdB subunit"
FT /id="PRO_0000157931"
FT HELIX 4..14
FT /evidence="ECO:0007829|PDB:6CON"
FT TURN 15..18
FT /evidence="ECO:0007829|PDB:6CON"
FT STRAND 23..26
FT /evidence="ECO:0007829|PDB:6CON"
FT HELIX 29..40
FT /evidence="ECO:0007829|PDB:6CON"
FT STRAND 51..58
FT /evidence="ECO:0007829|PDB:6CON"
FT STRAND 71..74
FT /evidence="ECO:0007829|PDB:6CON"
FT HELIX 77..86
FT /evidence="ECO:0007829|PDB:6CON"
FT STRAND 89..93
FT /evidence="ECO:0007829|PDB:6CON"
FT STRAND 96..99
FT /evidence="ECO:0007829|PDB:6CON"
FT STRAND 107..110
FT /evidence="ECO:0007829|PDB:6CON"
FT STRAND 116..118
FT /evidence="ECO:0007829|PDB:6CON"
FT HELIX 125..131
FT /evidence="ECO:0007829|PDB:6CON"
FT STRAND 132..140
FT /evidence="ECO:0007829|PDB:6CON"
FT TURN 143..145
FT /evidence="ECO:0007829|PDB:6CON"
FT STRAND 146..149
FT /evidence="ECO:0007829|PDB:6CON"
FT HELIX 158..160
FT /evidence="ECO:0007829|PDB:6CON"
FT HELIX 166..168
FT /evidence="ECO:0007829|PDB:6CON"
FT STRAND 173..185
FT /evidence="ECO:0007829|PDB:6CON"
FT HELIX 188..190
FT /evidence="ECO:0007829|PDB:6CON"
FT STRAND 193..197
FT /evidence="ECO:0007829|PDB:6CON"
FT HELIX 203..208
FT /evidence="ECO:0007829|PDB:6CON"
FT HELIX 228..236
FT /evidence="ECO:0007829|PDB:6CON"
FT HELIX 243..247
FT /evidence="ECO:0007829|PDB:6CON"
SQ SEQUENCE 250 AA; 27393 MW; 4278D0CDCBDCF6DE CRC64;
MSTRAEVCAV ACAELFRDAG EIMISPMTNM ASVGARLARL TFAPDILLTD GEAQLLADTP
ALGKTGAPNR IEGWMPFGRV FETLAWGRRH VVMGANQVDR YGNQNISAFG PLQRPTRQMF
GVRGSPGNTI NHATSYWVGN HCKRVFVEAV DVVSGIGYDK VDPDNPAFRF VNVYRVVSNL
GVFDFGGPDH SMRAVSLHPG VTPGDVRDAT SFEVHDLDAA EQTRLPTDDE LHLIRAVIDP
KSLRDREIRS
