IPDA_RHOJR
ID IPDA_RHOJR Reviewed; 296 AA.
AC Q0S7P9;
DT 07-APR-2021, integrated into UniProtKB/Swiss-Prot.
DT 05-SEP-2006, sequence version 1.
DT 25-MAY-2022, entry version 94.
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};
GN OrderedLocusNames=RHA1_ro04651 {ECO:0000312|EMBL:ABG96437.1};
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) OF 2-296 IN COMPLEXES WITH IPDB AND
RP COCHEA-COA AND OF MUTANT ALA-105 IN COMPLEX WITH IPDB AND COCHEA-COA,
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, AND
RP MUTAGENESIS OF GLU-105.
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 A family.
CC {ECO:0000305}.
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DR EMBL; CP000431; ABG96437.1; -; Genomic_DNA.
DR RefSeq; WP_011597005.1; NC_008268.1.
DR PDB; 6CO6; X-ray; 1.70 A; A=2-296.
DR PDB; 6CO9; X-ray; 1.60 A; A=2-296.
DR PDB; 6COJ; X-ray; 1.40 A; A=2-296.
DR PDBsum; 6CO6; -.
DR PDBsum; 6CO9; -.
DR PDBsum; 6COJ; -.
DR AlphaFoldDB; Q0S7P9; -.
DR SMR; Q0S7P9; -.
DR STRING; 101510.RHA1_ro04651; -.
DR EnsemblBacteria; ABG96437; ABG96437; RHA1_ro04651.
DR KEGG; rha:RHA1_ro04651; -.
DR PATRIC; fig|101510.16.peg.4694; -.
DR eggNOG; COG1788; Bacteria.
DR HOGENOM; CLU_049557_1_0_11; -.
DR OMA; YDPWFAK; -.
DR UniPathway; UPA01058; -.
DR Proteomes; UP000008710; Chromosome.
DR GO; GO:0008410; F:CoA-transferase activity; IEA:InterPro.
DR GO; GO:0016829; F:lyase activity; IEA:UniProtKB-KW.
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..296
FT /note="Cholesterol ring-cleaving hydrolase IpdA subunit"
FT /id="PRO_0000452313"
FT MUTAGEN 105
FT /note="E->A,D: Loss of activity."
FT /evidence="ECO:0000269|PubMed:29581275"
FT HELIX 11..16
FT /evidence="ECO:0007829|PDB:6COJ"
FT STRAND 23..26
FT /evidence="ECO:0007829|PDB:6COJ"
FT HELIX 36..44
FT /evidence="ECO:0007829|PDB:6COJ"
FT STRAND 49..57
FT /evidence="ECO:0007829|PDB:6COJ"
FT HELIX 58..65
FT /evidence="ECO:0007829|PDB:6COJ"
FT STRAND 69..77
FT /evidence="ECO:0007829|PDB:6COJ"
FT HELIX 87..94
FT /evidence="ECO:0007829|PDB:6COJ"
FT STRAND 98..102
FT /evidence="ECO:0007829|PDB:6COJ"
FT HELIX 105..116
FT /evidence="ECO:0007829|PDB:6COJ"
FT STRAND 120..125
FT /evidence="ECO:0007829|PDB:6COJ"
FT TURN 126..129
FT /evidence="ECO:0007829|PDB:6COJ"
FT HELIX 132..136
FT /evidence="ECO:0007829|PDB:6COJ"
FT HELIX 137..139
FT /evidence="ECO:0007829|PDB:6COJ"
FT STRAND 140..144
FT /evidence="ECO:0007829|PDB:6COJ"
FT STRAND 156..161
FT /evidence="ECO:0007829|PDB:6COJ"
FT STRAND 165..175
FT /evidence="ECO:0007829|PDB:6COJ"
FT HELIX 191..196
FT /evidence="ECO:0007829|PDB:6COJ"
FT STRAND 198..206
FT /evidence="ECO:0007829|PDB:6COJ"
FT HELIX 211..217
FT /evidence="ECO:0007829|PDB:6COJ"
FT HELIX 220..222
FT /evidence="ECO:0007829|PDB:6COJ"
FT STRAND 223..225
FT /evidence="ECO:0007829|PDB:6COJ"
FT HELIX 227..229
FT /evidence="ECO:0007829|PDB:6COJ"
FT STRAND 231..235
FT /evidence="ECO:0007829|PDB:6COJ"
FT TURN 237..242
FT /evidence="ECO:0007829|PDB:6COJ"
FT HELIX 253..262
FT /evidence="ECO:0007829|PDB:6COJ"
FT HELIX 266..276
FT /evidence="ECO:0007829|PDB:6COJ"
FT STRAND 277..279
FT /evidence="ECO:0007829|PDB:6COJ"
FT HELIX 281..294
FT /evidence="ECO:0007829|PDB:6COJ"
SQ SEQUENCE 296 AA; 32316 MW; BFA0D2EADE2619F0 CRC64;
MVSKRDKRIS LDDAVGELRS GMTIGIGGWG SRRKPMALVR ALLRSDVTDL TVVTYGGPDL
GLLCSAGKVT KAYYGFVSLD SAPFYDPWFA KARTAGEIAV REMDEGMVKC GLEAAAARLP
FLPIRAGLGS DVRRFWGDEL RTVTSPYPDA SGKSETLIAM PALNLDAALV HLNLGDKHGN
AAYTGVDPYF DDLYCAAAEK RFVSVERVVE TEELVKTVPL QNLILNRMMV DGVVEAPNGA
HFTLAGDSYG RDEKFQRHYA ESAKTPQAWQ QFVATYLSGS EDDYQAAVKK FAEEQA
