CHSE2_MYCTU
ID CHSE2_MYCTU Reviewed; 387 AA.
AC P71858; F2GEQ3; I6X7L6; O08027;
DT 30-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 2.
DT 03-AUG-2022, entry version 143.
DE RecName: Full=Acyl-CoA dehydrogenase FadE29 {ECO:0000303|PubMed:23560677};
DE Short=ACAD {ECO:0000303|PubMed:23560677};
DE EC=1.3.99.- {ECO:0000269|PubMed:23560677, ECO:0000269|PubMed:26161441};
DE AltName: Full=3-oxo-23,24-bisnorchol-4-en-22-oyl-CoA dehydrogenase beta subunit {ECO:0000305|PubMed:26161441};
DE AltName: Full=3-oxo-4-pregnene-20-carboxyl-CoA dehydrogenase beta subunit {ECO:0000305|PubMed:26161441};
GN Name=fadE29; OrderedLocusNames=Rv3543c;
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 INDUCTION.
RX PubMed=17635188; DOI=10.1111/j.1365-2958.2007.05827.x;
RA Kendall S.L., Withers M., Soffair C.N., Moreland N.J., Gurcha S.,
RA Sidders B., Frita R., Ten Bokum A., Besra G.S., Lott J.S., Stoker N.G.;
RT "A highly conserved transcriptional repressor controls a large regulon
RT involved in lipid degradation in Mycobacterium smegmatis and Mycobacterium
RT tuberculosis.";
RL Mol. Microbiol. 65:684-699(2007).
RN [3]
RP FUNCTION, SUBUNIT, PATHWAY, AND SUBSTRATE SPECIFICITY.
RC STRAIN=ATCC 27294 / TMC 102 / 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 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 [5]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF
RP GLU-241, COFACTOR, SUBUNIT, SUBSTRATE SPECIFICITY, AND ACTIVE SITE.
RC STRAIN=H37Rv;
RX PubMed=23560677; DOI=10.1021/bi4002979;
RA Thomas S.T., Sampson N.S.;
RT "Mycobacterium tuberculosis utilizes a unique heterotetrameric structure
RT for dehydrogenation of the cholesterol side chain.";
RL Biochemistry 52:2895-2904(2013).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RC STRAIN=H37Rv;
RX PubMed=26161441; DOI=10.1021/id500033m;
RA Yang M., Lu R., Guja K.E., Wipperman M.F., St Clair J.R., Bonds A.C.,
RA Garcia-Diaz M., Sampson N.S.;
RT "Unraveling cholesterol catabolism in Mycobacterium tuberculosis: ChsE4-
RT ChsE5 alpha2beta2 acyl-CoA dehydrogenase initiates beta-oxidation of 3-oxo-
RT cholest-4-en-26-oyl CoA.";
RL ACS Infect. Dis. 1:110-125(2015).
CC -!- FUNCTION: Involved in the third cycle of side chain dehydrogenation in
CC the beta-oxidation of cholesterol catabolism (PubMed:26161441).
CC Contributes partly to the virulence by increasing the efficiency of
CC beta-oxidation (PubMed:22045806, PubMed:23560677). Catalyzes the
CC dehydrogenation of 2'-propanoyl-CoA ester side chains of 3-oxo-4-
CC pregnene-20-carboxyl-CoA (3-OPC-CoA) to yield 3-oxo-4,17-pregnadiene-
CC 20-carboxyl-CoA (3-OPDC-CoA). Also able to dehydrogenate steroyl-CoA
CC such as 3-oxo-chol-4-en-24-oyl-CoA (3-OCO-CoA), 1beta-(2'-propanoyl-
CC CoA)-3a-alpha-H- 7a-beta-methylhexahydro-4-indanone (indanone-CoA
CC ester), hexahydroindanone and pregenenone (PubMed:22045806,
CC PubMed:23560677). {ECO:0000269|PubMed:22045806,
CC ECO:0000269|PubMed:23560677, ECO:0000269|PubMed:26161441}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-oxochol-4-en-22-oyl-CoA + A = 3-oxochola-4,17-dien-22-oyl-
CC CoA + AH2; Xref=Rhea:RHEA:46324, ChEBI:CHEBI:13193,
CC ChEBI:CHEBI:17499, ChEBI:CHEBI:83792, ChEBI:CHEBI:86020;
CC Evidence={ECO:0000269|PubMed:23560677, ECO:0000269|PubMed:26161441};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000269|PubMed:23560677};
CC Note=Binds 1 FAD per heterodimer. {ECO:0000269|PubMed:23560677};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=5.3 uM for 3-OPC-CoA (at pH 8.5 and 25 degrees Celsius)
CC {ECO:0000269|PubMed:23560677, ECO:0000269|PubMed:26161441};
CC KM=6.5 uM for 3-OCO-CoA (at pH 8.5 and 25 degrees Celsius)
CC {ECO:0000269|PubMed:26161441};
CC KM=86 uM for indanone-CoA ester (at pH 8.5 and 25 degrees Celsius)
CC {ECO:0000269|PubMed:23560677};
CC Note=kcat is 78 min(-1) for 3-OPC-CoA as substrate (at pH 8.5 and 25
CC degrees Celsius) (PubMed:23560677). kcat is 5.1 min(-1) for indanone-
CC CoA ester as substrate (at pH 8.5 and 25 degrees Celsius)
CC (PubMed:23560677). kcat is 1.3 sec(-1) for 3-OPC-CoA as substrate (at
CC pH 8.5 and 25 degrees Celsius) (PubMed:26161441). kcat is 0.16 sec(-
CC 1) for 3-OCO-CoA as substrate (at pH 8.5 and 25 degrees Celsius)
CC (PubMed:26161441). {ECO:0000269|PubMed:23560677,
CC ECO:0000269|PubMed:26161441};
CC -!- PATHWAY: Steroid metabolism; cholesterol degradation.
CC {ECO:0000305|PubMed:22045806}.
CC -!- SUBUNIT: Heterotetramer composed of FadE28 and FadE29.
CC {ECO:0000269|PubMed:22045806, ECO:0000269|PubMed:23560677}.
CC -!- INDUCTION: Induced by cholesterol and repressed by KtsR.
CC {ECO:0000269|PubMed:17635188}.
CC -!- SIMILARITY: Belongs to the acyl-CoA dehydrogenase family.
CC {ECO:0000305}.
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DR EMBL; AL123456; CCP46365.1; -; Genomic_DNA.
DR RefSeq; NP_218060.1; NC_000962.3.
DR RefSeq; WP_003419296.1; NZ_NVQJ01000014.1.
DR AlphaFoldDB; P71858; -.
DR SMR; P71858; -.
DR STRING; 83332.Rv3543c; -.
DR PaxDb; P71858; -.
DR DNASU; 888131; -.
DR GeneID; 45427527; -.
DR GeneID; 888131; -.
DR KEGG; mtu:Rv3543c; -.
DR PATRIC; fig|83332.111.peg.3948; -.
DR TubercuList; Rv3543c; -.
DR eggNOG; COG1960; Bacteria.
DR InParanoid; P71858; -.
DR OMA; VEQQIFV; -.
DR PhylomeDB; P71858; -.
DR BioCyc; MetaCyc:G185E-7820-MON; -.
DR UniPathway; UPA01058; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0071949; F:FAD binding; IDA:UniProtKB.
DR GO; GO:0016627; F:oxidoreductase activity, acting on the CH-CH group of donors; IEA:InterPro.
DR GO; GO:0051701; P:biological process involved in interaction with host; IMP:MTBBASE.
DR GO; GO:0006707; P:cholesterol catabolic process; NAS:UniProtKB.
DR GO; GO:0033539; P:fatty acid beta-oxidation using acyl-CoA dehydrogenase; IDA:UniProtKB.
DR Gene3D; 1.10.540.10; -; 1.
DR Gene3D; 2.40.110.10; -; 1.
DR InterPro; IPR006091; Acyl-CoA_Oxase/DH_mid-dom.
DR InterPro; IPR046373; Acyl-CoA_Oxase/DH_mid-dom_sf.
DR InterPro; IPR036250; AcylCo_DH-like_C.
DR InterPro; IPR009075; AcylCo_DH/oxidase_C.
DR InterPro; IPR013786; AcylCoA_DH/ox_N.
DR InterPro; IPR037069; AcylCoA_DH/ox_N_sf.
DR InterPro; IPR009100; AcylCoA_DH/oxidase_NM_dom.
DR Pfam; PF00441; Acyl-CoA_dh_1; 1.
DR Pfam; PF02770; Acyl-CoA_dh_M; 1.
DR Pfam; PF02771; Acyl-CoA_dh_N; 1.
DR SUPFAM; SSF47203; SSF47203; 1.
DR SUPFAM; SSF56645; SSF56645; 1.
PE 1: Evidence at protein level;
KW Cholesterol metabolism; FAD; Flavoprotein; Lipid degradation;
KW Lipid metabolism; NAD; NADP; Oxidoreductase; Reference proteome;
KW Steroid metabolism; Sterol metabolism; Virulence.
FT CHAIN 1..387
FT /note="Acyl-CoA dehydrogenase FadE29"
FT /id="PRO_0000438518"
FT ACT_SITE 241
FT /note="Proton acceptor"
FT /evidence="ECO:0000305|PubMed:23560677"
FT BINDING 123..126
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:I6YCA3"
FT BINDING 132
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:I6YCA3"
FT BINDING 158
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:I6YCA3"
FT BINDING 367..369
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:I6YCA3"
FT MUTAGEN 241
FT /note="E->Q: Unable to dehydrogenate pregnene-carboxyl-CoA
FT ester."
FT /evidence="ECO:0000269|PubMed:23560677"
SQ SEQUENCE 387 AA; 42715 MW; ACCBA65235DC57A8 CRC64;
MFIDLTPEQR QLQAEIRQYF SNLISPDERT EMEKDRHGPA YRAVIRRMGR DGRLGVGWPK
EFGGLGFGPI EQQIFVNEAH RADVPLPAVT LQTVGPTLQA HGSELQKKKF LPAILAGEAH
FAIGYTEPEA GTDLASLRTT AVRDGDHYIV NGQKVFTTGA HDADYIWLAC RTDPNAAKHK
GISILIVDTK DPGYSWTPII LADGAHHTNA TYYNDVRVPV DMLVGKENDG WRLITTQLNN
ERVMLGPAGR FASIYDRVHA WASVPGGNGV TPIDHDDVKR ALGEIRAIWR INELLNWQVA
SAGEDINMAD AAATKVFGTE RVQRAGRLAE EIVGKYGNPA EPDTAELLRW LDAQTKRNLV
ITFGGGVNEV MREMIAASGL KVPRVPR
