IPDB_RHOJR
ID IPDB_RHOJR Reviewed; 253 AA.
AC Q0S7Q0;
DT 07-APR-2021, integrated into UniProtKB/Swiss-Prot.
DT 05-SEP-2006, sequence version 1.
DT 25-MAY-2022, entry version 84.
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};
GN OrderedLocusNames=RHA1_ro04650 {ECO:0000312|EMBL:ABG96436.1};
OS Rhodococcus jostii (strain RHA1).
OC Bacteria; Actinobacteria; Corynebacteriales; Nocardiaceae; Rhodococcus.
OX NCBI_TaxID=101510;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=RHA1;
RX PubMed=17030794; DOI=10.1073/pnas.0607048103;
RA McLeod M.P., Warren R.L., Hsiao W.W.L., Araki N., Myhre M., Fernandes C.,
RA Miyazawa D., Wong W., Lillquist A.L., Wang D., Dosanjh M., Hara H.,
RA Petrescu A., Morin R.D., Yang G., Stott J.M., Schein J.E., Shin H.,
RA Smailus D., Siddiqui A.S., Marra M.A., Jones S.J.M., Holt R.,
RA Brinkman F.S.L., Miyauchi K., Fukuda M., Davies J.E., Mohn W.W.,
RA Eltis L.D.;
RT "The complete genome of Rhodococcus sp. RHA1 provides insights into a
RT catabolic powerhouse.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:15582-15587(2006).
RN [2]
RP FUNCTION, PATHWAY, AND DISRUPTION PHENOTYPE.
RC STRAIN=RHA1;
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 [3] {ECO:0007744|PDB:6CO6, ECO:0007744|PDB:6CO9, ECO:0007744|PDB:6COJ}
RP X-RAY CRYSTALLOGRAPHY (1.40 ANGSTROMS) IN COMPLEXES WITH IPDB AND
RP COCHEA-COA, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES,
RP SUBUNIT, AND MUTAGENESIS OF GLU-58; ARG-92 AND ARG-126.
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, PubMed:29581275). Opens the last steroid
CC ring of 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) (Probable)
CC (PubMed:29581275). {ECO:0000269|PubMed:28377529,
CC ECO:0000269|PubMed:29581275, ECO:0000305|PubMed:28377529}.
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 -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=120 uM for COCHEA-CoA {ECO:0000269|PubMed:29581275};
CC Note=kcat is 5.8 sec(-1) with COCHEA-CoA as substrate.
CC {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 or HIP, but grows as the wild-type on pyruvate. In the
CC presence of cholesterol, ipdAB double deletion mutant accumulates
CC COCHEA-CoA. {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; CP000431; ABG96436.1; -; Genomic_DNA.
DR RefSeq; WP_011597004.1; NC_008268.1.
DR PDB; 6CO6; X-ray; 1.70 A; B=1-253.
DR PDB; 6CO9; X-ray; 1.60 A; B=1-253.
DR PDB; 6COJ; X-ray; 1.40 A; B=1-253.
DR PDBsum; 6CO6; -.
DR PDBsum; 6CO9; -.
DR PDBsum; 6COJ; -.
DR AlphaFoldDB; Q0S7Q0; -.
DR SMR; Q0S7Q0; -.
DR STRING; 101510.RHA1_ro04650; -.
DR EnsemblBacteria; ABG96436; ABG96436; RHA1_ro04650.
DR KEGG; rha:RHA1_ro04650; -.
DR PATRIC; fig|101510.16.peg.4693; -.
DR eggNOG; COG2057; Bacteria.
DR HOGENOM; CLU_069088_0_0_11; -.
DR OMA; YWVGNHS; -.
DR UniPathway; UPA01058; -.
DR Proteomes; UP000008710; Chromosome.
DR GO; GO:0016829; F:lyase activity; IEA:UniProtKB-KW.
DR GO; GO:0006707; P:cholesterol catabolic process; IEA:UniProtKB-UniPathway.
DR InterPro; IPR037171; NagB/RpiA_transferase-like.
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..253
FT /note="Cholesterol ring-cleaving hydrolase IpdB subunit"
FT /id="PRO_0000452314"
FT MUTAGEN 58
FT /note="E->A: 20% decrease in activity."
FT /evidence="ECO:0000269|PubMed:29581275"
FT MUTAGEN 92
FT /note="R->M: Loss of activity."
FT /evidence="ECO:0000269|PubMed:29581275"
FT MUTAGEN 126
FT /note="R->M: Loss of activity."
FT /evidence="ECO:0000269|PubMed:29581275"
FT HELIX 10..20
FT /evidence="ECO:0007829|PDB:6COJ"
FT TURN 21..24
FT /evidence="ECO:0007829|PDB:6COJ"
FT STRAND 27..32
FT /evidence="ECO:0007829|PDB:6COJ"
FT HELIX 35..46
FT /evidence="ECO:0007829|PDB:6COJ"
FT STRAND 57..64
FT /evidence="ECO:0007829|PDB:6COJ"
FT STRAND 74..77
FT /evidence="ECO:0007829|PDB:6COJ"
FT HELIX 80..89
FT /evidence="ECO:0007829|PDB:6COJ"
FT STRAND 92..96
FT /evidence="ECO:0007829|PDB:6COJ"
FT STRAND 99..101
FT /evidence="ECO:0007829|PDB:6COJ"
FT STRAND 110..113
FT /evidence="ECO:0007829|PDB:6COJ"
FT STRAND 119..121
FT /evidence="ECO:0007829|PDB:6COJ"
FT HELIX 128..134
FT /evidence="ECO:0007829|PDB:6COJ"
FT STRAND 137..143
FT /evidence="ECO:0007829|PDB:6COJ"
FT TURN 146..148
FT /evidence="ECO:0007829|PDB:6COJ"
FT HELIX 161..163
FT /evidence="ECO:0007829|PDB:6COJ"
FT HELIX 169..171
FT /evidence="ECO:0007829|PDB:6COJ"
FT STRAND 176..190
FT /evidence="ECO:0007829|PDB:6COJ"
FT TURN 191..193
FT /evidence="ECO:0007829|PDB:6COJ"
FT STRAND 194..200
FT /evidence="ECO:0007829|PDB:6COJ"
FT HELIX 206..211
FT /evidence="ECO:0007829|PDB:6COJ"
FT HELIX 220..222
FT /evidence="ECO:0007829|PDB:6COJ"
FT HELIX 231..239
FT /evidence="ECO:0007829|PDB:6COJ"
FT HELIX 246..250
FT /evidence="ECO:0007829|PDB:6COJ"
SQ SEQUENCE 253 AA; 27507 MW; 92C13C2F6AAC0B90 CRC64;
MSETITEVTR AEYCAIACAD IFSGAGEIMA SPMATLPLIG ARLARLTTEP DLLITDGEAL
IFADTPAVGA KAPIEGWMPF RKVFDVVASG RRHVVMGANQ IDRHGNQNLS AFGPLQQPTR
QMFGVRGAPG NTINHPTSYW VGKHTSRVFC DTVDIVSGVG YDQIDPENPA YRFHHLHRVV
SNLGVFDFGG PDHTFRALSL HPGVTADQVA DNTSFEVAGL ADAGVTREPT DEELRLIREV
LDPRSLRDRE VSV
