LTP2_MYCTU
ID LTP2_MYCTU Reviewed; 386 AA.
AC I6Y3T7;
DT 07-APR-2021, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2012, sequence version 1.
DT 03-AUG-2022, entry version 59.
DE RecName: Full=17-hydroxy-3-oxo-4-pregnene-20-carboxyl-CoA lyase {ECO:0000305};
DE EC=4.1.3.- {ECO:0000269|PubMed:29109182, ECO:0000269|PubMed:31568719};
DE AltName: Full=Retro-aldolase Ltp2 {ECO:0000305};
GN Name=ltp2 {ECO:0000303|PubMed:22045806};
GN OrderedLocusNames=Rv3540c {ECO:0000312|EMBL:CCP46362.1};
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 FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, PATHWAY,
RP SUBUNIT, AND INTERACTION WITH CHSH2.
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, SAXS AND EM STUDIES OF THE
RP CHSH1-CHSH2-LTP2 COMPLEX, AND MUTAGENESIS OF CYS-85 AND HIS-344.
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).
CC -!- FUNCTION: Involved in cholesterol side chain degradation
CC (PubMed:22045806, PubMed:29109182). When associated with the
CC ChsH1/ChsH2 hydratase, catalyzes the retroaldol cleavage of 17-hydroxy-
CC 3-oxo-4-pregnene-20-carboxyl-CoA (17-HOPC-CoA) produced by the
CC hydratase, forming androst-4-ene-3,17-dione and propionyl-CoA
CC (PubMed:29109182, PubMed:31568719). {ECO:0000269|PubMed:22045806,
CC ECO:0000269|PubMed:29109182, ECO:0000269|PubMed:31568719}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=17-hydroxy-3-oxochol-4-en-22-oyl-CoA = androst-4-ene-3,17-
CC dione + propanoyl-CoA; Xref=Rhea:RHEA:46648, ChEBI:CHEBI:16422,
CC ChEBI:CHEBI:57392, ChEBI:CHEBI:86028;
CC Evidence={ECO:0000269|PubMed:29109182, ECO:0000269|PubMed:31568719};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46649;
CC Evidence={ECO:0000269|PubMed:29109182, ECO:0000269|PubMed:31568719};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=6.54 uM for 17-HOPC-CoA (in the presence of ChsH2-DUF35)
CC {ECO:0000269|PubMed:29109182};
CC Note=kcat is 159 sec(-1). {ECO:0000269|PubMed:29109182};
CC -!- PATHWAY: Steroid metabolism; cholesterol degradation.
CC {ECO:0000269|PubMed:22045806, ECO:0000269|PubMed:29109182}.
CC -!- SUBUNIT: Homodimer (PubMed:29109182). Interacts with the ChsH1/ChsH2
CC hydratase via the DUF35 C-terminal region of ChsH2 (ChsH2-DUF35)
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:29109182, ECO:0000269|PubMed:31568719}.
CC -!- SIMILARITY: Belongs to the thiolase-like superfamily. {ECO:0000305}.
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DR EMBL; AL123456; CCP46362.1; -; Genomic_DNA.
DR RefSeq; NP_218057.1; NC_000962.3.
DR RefSeq; WP_003419287.1; NZ_NVQJ01000014.1.
DR AlphaFoldDB; I6Y3T7; -.
DR SMR; I6Y3T7; -.
DR STRING; 83332.Rv3540c; -.
DR PaxDb; I6Y3T7; -.
DR DNASU; 888450; -.
DR GeneID; 45427524; -.
DR GeneID; 888450; -.
DR KEGG; mtu:Rv3540c; -.
DR PATRIC; fig|83332.111.peg.3945; -.
DR TubercuList; Rv3540c; -.
DR eggNOG; COG0183; Bacteria.
DR OMA; SSPDQYT; -.
DR PhylomeDB; I6Y3T7; -.
DR BioCyc; MetaCyc:G185E-7817-MON; -.
DR UniPathway; UPA01058; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0016747; F:acyltransferase activity, transferring groups other than amino-acyl groups; IEA:InterPro.
DR GO; GO:0016829; F:lyase activity; IEA:UniProtKB-KW.
DR GO; GO:0006707; P:cholesterol catabolic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 3.40.47.10; -; 1.
DR InterPro; IPR002155; Thiolase.
DR InterPro; IPR016039; Thiolase-like.
DR PIRSF; PIRSF000429; Ac-CoA_Ac_transf; 1.
DR SUPFAM; SSF53901; SSF53901; 2.
PE 1: Evidence at protein level;
KW Cholesterol metabolism; Lipid metabolism; Lyase; Reference proteome;
KW Steroid metabolism; Sterol metabolism.
FT CHAIN 1..386
FT /note="17-hydroxy-3-oxo-4-pregnene-20-carboxyl-CoA lyase"
FT /id="PRO_0000452243"
FT ACT_SITE 292
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:D1AB74"
FT ACT_SITE 342
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:D1AB74"
FT MUTAGEN 85
FT /note="C->A: No change in activity."
FT /evidence="ECO:0000269|PubMed:31568719"
FT MUTAGEN 344
FT /note="H->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:31568719"
SQ SEQUENCE 386 AA; 40588 MW; 0802AD8CE32493AB CRC64;
MLSGQAAIVG IGATDFSKNS GRSELRLAAE AVLDALADAG LSPTDVDGLT TFTMDTNTEI
AVARAAGIGE LTFFSKIHYG GGAACATVQH AAMAVATGVA DVVVAYRAFN ERSGMRFGQV
QTRLTENADS TGVDNSFSYP HGLSTPAAQV AMIARRYMHL SGATSRDFGA VSVADRKHAA
NNPKAYFYGK PITIEDHQNS RWIAEPLRLL DCCQETDGAV AIVVTSAARA RDLKQRPVVI
EAAAQGCSPD QYTMVSYYRP ELDGLPEMGL VGRQLWAQSG LTPADVQTAV LYDHFTPFTL
IQLEELGFCG KGEAKDFIAD GAIEVGGRLP INTHGGQLGE AYIHGMNGIA EGVRQLRGTS
VNPVAGVEHV LVTAGTGVPT SGLILG
