CHSE1_MYCTU
ID CHSE1_MYCTU Reviewed; 339 AA.
AC P71857; I6YCD6;
DT 30-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 3.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Acyl-CoA dehydrogenase FadE28 {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 alpha subunit {ECO:0000305|PubMed:23560677};
DE AltName: Full=3-oxo-4-pregnene-20-carboxyl-CoA dehydrogenase alpha subunit {ECO:0000305|PubMed:23560677};
GN Name=fadE28; OrderedLocusNames=Rv3544c; ORFNames=LH57_19335;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 27294 / TMC 102 / H37Rv;
RA Hazbon M.H., Riojas M.A., Damon A.M., Alalade R.O., Cantwell B.J.,
RA Monaco A., King S., Sohrabi A.;
RT "Phylogenetic analysis of Mycobacterial species using whole genome
RT sequences.";
RL Submitted (SEP-2014) to the EMBL/GenBank/DDBJ databases.
RN [3]
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 [4]
RP FUNCTION, AND INDUCTION.
RC STRAIN=ATCC 27294 / TMC 102 / H37Rv;
RX PubMed=18486437; DOI=10.1016/j.micpath.2008.01.006;
RA Lam T.H., Yuen K.Y., Ho P.L., Wong K.C., Leong W.M., Law H.K., Weng X.H.,
RA Zhang W.H., Chen S., Yam W.C.;
RT "Differential fadE28 expression associated with phenotypic virulence of
RT Mycobacterium tuberculosis.";
RL Microb. Pathog. 45:12-17(2008).
RN [5]
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 [6]
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 [7]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR,
RP SUBUNIT, AND SUBSTRATE SPECIFICITY.
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 [8]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
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). May
CC play an important role for the initial macrophage invasion, possibly in
CC response to the acidification of phagosome (PubMed:18486437). It
CC contributes partly to the virulence by increasing the efficiency of
CC beta-oxidation (PubMed:18486437, PubMed:22045806). 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, PubMed:26161441). {ECO:0000269|PubMed:18486437,
CC ECO:0000269|PubMed:22045806, ECO:0000269|PubMed:23560677,
CC 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 pH dependence:
CC Optimum pH is above 8. No activity is observed under pH 6.
CC {ECO:0000269|PubMed:23560677};
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 (PubMed:17635188). Up-regulated in vitro by acid shock and ex vivo by
CC macrophage challenge (PubMed:18486437). {ECO:0000269|PubMed:17635188,
CC ECO:0000269|PubMed:18486437}.
CC -!- SIMILARITY: Belongs to the acyl-CoA dehydrogenase family.
CC {ECO:0000305}.
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DR EMBL; CP009480; AIR16334.1; -; Genomic_DNA.
DR EMBL; AL123456; CCP46366.1; -; Genomic_DNA.
DR RefSeq; NP_218061.1; NC_000962.3.
DR RefSeq; WP_003419299.1; NZ_NVQJ01000014.1.
DR AlphaFoldDB; P71857; -.
DR SMR; P71857; -.
DR STRING; 83332.Rv3544c; -.
DR PaxDb; P71857; -.
DR DNASU; 888091; -.
DR GeneID; 45427528; -.
DR GeneID; 888091; -.
DR KEGG; mtu:Rv3544c; -.
DR PATRIC; fig|83332.111.peg.3949; -.
DR TubercuList; Rv3544c; -.
DR eggNOG; COG1960; Bacteria.
DR HOGENOM; CLU_018204_5_3_11; -.
DR OMA; DITYPMH; -.
DR PhylomeDB; P71857; -.
DR BioCyc; MetaCyc:G185E-7821-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 GO; GO:0009268; P:response to pH; IEP:MTBBASE.
DR Gene3D; 1.10.540.10; -; 1.
DR Gene3D; 2.40.110.10; -; 1.
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; 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..339
FT /note="Acyl-CoA dehydrogenase FadE28"
FT /id="PRO_0000438517"
FT BINDING 227
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000305|PubMed:23560677"
FT BINDING 238
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000305|PubMed:23560677"
FT BINDING 295
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:I6Y3Q0"
FT BINDING 299
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:I6Y3Q0"
SQ SEQUENCE 339 AA; 35469 MW; D84AC763D7ACFE5F CRC64;
MDFDPTAEQQ AVADVVTSVL ERDISWEALV CGGVTALPVP ERLGGDGVGL FEVGALLTEV
GRHGAVTPAL ATLGLGVVPL LELASAEQQD RFLAGVAKGG VLTAALNEPG AALPDRPATS
FVGGRLSGTK VGVGYAEQAD WMLVTADNAV VVVSPTADGV RMVRTPTSNG SDEYVMTMDG
VAVADCDILA DVAAHRVNQL ALAVMGAYAD GLVAGALRLT ADYVANRKQF GKPLSTFQTV
AAQLAEVYIA SRTIDLVAKS VIWRLAEDLD AGDDLGVLGY WVTSQAPPAM QICHHLHGGM
GMDVTYPMHR YYSTIKDLTR LLGGPSHRLE LLGARCSLT
