CHSH2_MYCTU
ID CHSH2_MYCTU Reviewed; 311 AA.
AC I6YGF8;
DT 07-APR-2021, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2012, sequence version 1.
DT 03-AUG-2022, entry version 60.
DE RecName: Full=3-oxo-4,17-pregnadiene-20-carboxyl-CoA hydratase alpha subunit {ECO:0000305};
DE EC=4.2.1.- {ECO:0000269|PubMed:25203216, ECO:0000269|PubMed:31568719};
DE AltName: Full=Enoyl-CoA hydratase alpha subunit {ECO:0000305};
GN Name=chsH2 {ECO:0000303|PubMed:25203216};
GN OrderedLocusNames=Rv3542c {ECO:0000312|EMBL:CCP46364.1};
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, AND PATHWAY.
RC STRAIN=H37Rv;
RX PubMed=22045806; DOI=10.1074/jbc.m111.313643;
RA Thomas S.T., VanderVen B.C., Sherman D.R., Russell D.G., Sampson N.S.;
RT "Pathway profiling in Mycobacterium tuberculosis: elucidation of
RT cholesterol-derived catabolite and enzymes that catalyze its metabolism.";
RL J. Biol. Chem. 286:43668-43678(2011).
RN [4]
RP ACTIVITY REGULATION, INTERACTION WITH LTP2, AND DOMAIN.
RX PubMed=29109182; DOI=10.1128/jb.00512-17;
RA Gilbert S., Hood L., Seah S.Y.K.;
RT "Characterization of an aldolase involved in cholesterol side chain
RT degradation in Mycobacterium tuberculosis.";
RL J. Bacteriol. 200:e00512-e00512(2018).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, AND SAXS AND EM STUDIES OF THE
RP CHSH1-CHSH2-LTP2 COMPLEX.
RC STRAIN=H37Rv;
RX PubMed=31568719; DOI=10.1021/acs.biochem.9b00673;
RA Yuan T., Yang M., Gehring K., Sampson N.S.;
RT "Mycobacterium tuberculosis exploits a heterohexameric enoyl-CoA hydratase
RT retro-aldolase complex for cholesterol catabolism.";
RL Biochemistry 58:4224-4235(2019).
RN [6] {ECO:0007744|PDB:4W78, ECO:0007744|PDB:4WNB}
RP X-RAY CRYSTALLOGRAPHY (1.54 ANGSTROMS) OF 1-187 IN COMPLEXES WITH CHSH1 AND
RP SUBSTRATE ANALOG, FUNCTION, CATALYTIC ACTIVITY, PATHWAY, SUBUNIT, AND
RP DOMAIN.
RC STRAIN=H37Rv;
RX PubMed=25203216; DOI=10.1021/cb500232h;
RA Yang M., Guja K.E., Thomas S.T., Garcia-Diaz M., Sampson N.S.;
RT "A distinct MaoC-like enoyl-CoA hydratase architecture mediates cholesterol
RT catabolism in Mycobacterium tuberculosis.";
RL ACS Chem. Biol. 9:2632-2645(2014).
CC -!- FUNCTION: Involved in cholesterol side chain degradation
CC (PubMed:22045806, PubMed:25203216). Catalyzes the hydration of 3-oxo-
CC 4,17-pregnadiene-20-carboxyl-CoA (3-OPDC-CoA) to form 17-hydroxy-3-oxo-
CC 4-pregnene-20-carboxyl-CoA (17-HOPC-CoA), in the modified beta-
CC oxidation pathway for cholesterol side chain degradation
CC (PubMed:25203216, PubMed:31568719). Can also use octenoyl-CoA and
CC decenoyl-CoA, with lower efficiency (PubMed:25203216).
CC {ECO:0000269|PubMed:22045806, ECO:0000269|PubMed:25203216,
CC ECO:0000269|PubMed:31568719}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-oxochola-4,17-dien-22-oyl-CoA + H2O = 17-hydroxy-3-oxochol-
CC 4-en-22-oyl-CoA; Xref=Rhea:RHEA:46336, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:86020, ChEBI:CHEBI:86028;
CC Evidence={ECO:0000269|PubMed:25203216, ECO:0000269|PubMed:31568719};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46337;
CC Evidence={ECO:0000269|PubMed:25203216, ECO:0000269|PubMed:31568719};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E)-octenoyl-CoA + H2O = 3-hydroxyoctanoyl-CoA;
CC Xref=Rhea:RHEA:46348, ChEBI:CHEBI:15377, ChEBI:CHEBI:62242,
CC ChEBI:CHEBI:86040; Evidence={ECO:0000269|PubMed:25203216};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E)-decenoyl-CoA + H2O = 3-hydroxydecanoyl-CoA;
CC Xref=Rhea:RHEA:46352, ChEBI:CHEBI:15377, ChEBI:CHEBI:61406,
CC ChEBI:CHEBI:86041; Evidence={ECO:0000269|PubMed:25203216};
CC -!- ACTIVITY REGULATION: In the absence of the Ltp2 aldolase, ChsH1/ChsH2
CC can hydrate only about 30% of the 3-OPDC-CoA substrate. Complete
CC turnover requires the presence of Ltp2. {ECO:0000269|PubMed:29109182}.
CC -!- PATHWAY: Steroid metabolism; cholesterol degradation.
CC {ECO:0000269|PubMed:22045806, ECO:0000269|PubMed:25203216}.
CC -!- SUBUNIT: Heterodimer composed of ChsH1 and ChsH2. Two heterodimers
CC combine to form an heterotetramer (PubMed:25203216). The complex
CC interacts with Ltp2 via the DUF35 C-terminal region of ChsH2
CC (PubMed:29109182, PubMed:31568719). The ChsH1-ChsH2-Ltp2 protein
CC complex is composed of two protomers that form a heterohexameric
CC structure through the Ltp2 dimerization interface (PubMed:31568719).
CC {ECO:0000269|PubMed:25203216, ECO:0000269|PubMed:29109182,
CC ECO:0000269|PubMed:31568719}.
CC -!- DOMAIN: The DUF35 C-terminal region is not required for hydratase
CC activity (PubMed:25203216). This region is involved in interaction with
CC LtpA and is required for optimal LtpA aldolase activity
CC (PubMed:29109182). {ECO:0000269|PubMed:25203216,
CC ECO:0000269|PubMed:29109182}.
CC -!- SIMILARITY: Belongs to the thioester dehydratase family. {ECO:0000305}.
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DR EMBL; AL123456; CCP46364.1; -; Genomic_DNA.
DR RefSeq; NP_218059.1; NC_000962.3.
DR RefSeq; WP_003419293.1; NZ_NVQJ01000014.1.
DR PDB; 4W78; X-ray; 1.54 A; A/C/E/G=3-180.
DR PDB; 4WNB; X-ray; 1.76 A; A=1-187.
DR PDBsum; 4W78; -.
DR PDBsum; 4WNB; -.
DR AlphaFoldDB; I6YGF8; -.
DR SMR; I6YGF8; -.
DR STRING; 83332.Rv3542c; -.
DR PaxDb; I6YGF8; -.
DR DNASU; 888486; -.
DR GeneID; 888486; -.
DR KEGG; mtu:Rv3542c; -.
DR PATRIC; fig|83332.111.peg.3947; -.
DR TubercuList; Rv3542c; -.
DR eggNOG; COG1545; Bacteria.
DR OMA; WRIMKFR; -.
DR BioCyc; MetaCyc:G185E-7819-MON; -.
DR UniPathway; UPA01058; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0016829; F:lyase activity; IEA:UniProtKB-KW.
DR GO; GO:0006707; P:cholesterol catabolic process; IEA:UniProtKB-UniPathway.
DR InterPro; IPR002878; DUF35_OB-fold_C.
DR InterPro; IPR029069; HotDog_dom_sf.
DR InterPro; IPR039569; MaoC-like_dehydrat_N.
DR InterPro; IPR012340; NA-bd_OB-fold.
DR Pfam; PF13452; MaoC_dehydrat_N; 1.
DR Pfam; PF01796; OB_aCoA_assoc; 1.
DR SUPFAM; SSF50249; SSF50249; 1.
DR SUPFAM; SSF54637; SSF54637; 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..311
FT /note="3-oxo-4,17-pregnadiene-20-carboxyl-CoA hydratase
FT alpha subunit"
FT /id="PRO_0000452241"
FT REGION 198..295
FT /note="DUF35"
FT /evidence="ECO:0000305"
SQ SEQUENCE 311 AA; 33972 MW; C2C5939949A67A5A CRC64;
MTGVSDIQEA VAQIKAAGPS KPRLARDPVN QPMINNWVEA IGDRNPIYVD DAAARAAGHP
GIVAPPAMIQ VWTMMGLGGV RPKDDPLGPI IKLFDDAGYI GVVATNCEQT YHRYLLPGEQ
VSISAELGDV VGPKQTALGE GWFINQHIVW QVGDEDVAEM NWRILKFKPA GSPSSVPDDL
DPDAMMRPSS SRDTAFFWDG VKAHELRIQR LADGSLRHPP VPAVWQDKSV PINYVVSSGR
GTVFSFVVHH APKVPGRTVP FVIALVELEE GVRMLGELRG ADPARVAIGM PVRATYIDFP
DWSLYAWEPD E
