CHSE3_MYCTU
ID CHSE3_MYCTU Reviewed; 711 AA.
AC P96855; F2GJR9; I6YCG5;
DT 30-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 2.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Acyl-CoA dehydrogenase FadE34 {ECO:0000303|PubMed:26161441};
DE Short=ACAD {ECO:0000303|PubMed:26161441};
DE EC=1.3.99.- {ECO:0000269|PubMed:25645564, ECO:0000269|PubMed:26161441};
DE AltName: Full=3-oxochol-4-en-24-oyl-CoA dehydrogenase {ECO:0000305|PubMed:26161441};
GN Name=fadE34; Synonyms=chsE3 {ECO:0000303|PubMed:26161441};
GN OrderedLocusNames=Rv3573c;
GN ORFNames=LH57_19490 {ECO:0000312|EMBL:AIR16364.1};
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 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.
RC STRAIN=ATCC 25618 / H37Rv;
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 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, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES,
RP SUBUNIT, DOMAIN, AND MUTAGENESIS OF ARG-236 AND GLU-581.
RC STRAIN=H37Rv;
RX PubMed=25645564; DOI=10.1128/jb.02420-14;
RA Ruprecht A., Maddox J., Stirling A.J., Visaggio N., Seah S.Y.;
RT "Characterization of novel acyl coenzyme A dehydrogenases involved in
RT bacterial steroid degradation.";
RL J. Bacteriol. 197:1360-1367(2015).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR,
RP PATHWAY, AND SUBUNIT.
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 second cycle of side chain dehydrogenation in
CC the beta-oxidation of cholesterol catabolism. It contributes partly to
CC the virulence by increasing the efficiency of beta-oxidation
CC (PubMed:26161441). Catalyzes the dehydrogenation of the five-carbon
CC steroid side chain of 3-oxo-chol-4-en-24-oyl-CoA (3-OCO-CoA) to yield
CC 3-oxochol-4,22-dien-24-oyl-CoA (PubMed:26161441). Can also use 3beta-
CC hydroxy-chol-5-ene-24-oyl-CoA, and shows weak activity with cholyl-CoA
CC and deoxycholyl-CoA (PubMed:25645564). {ECO:0000269|PubMed:25645564,
CC ECO:0000269|PubMed:26161441}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-oxochol-4-en-24-oyl-CoA + A = (22E)-3-oxo-chol-4,22-dien-24-
CC oyl-CoA + AH2; Xref=Rhea:RHEA:46684, ChEBI:CHEBI:13193,
CC ChEBI:CHEBI:17499, ChEBI:CHEBI:86412, ChEBI:CHEBI:136759;
CC Evidence={ECO:0000269|PubMed:26161441};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46685;
CC Evidence={ECO:0000269|PubMed:26161441};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3beta-hydroxy-chol-5-ene-24-oyl-CoA + A = 3beta-hydroxy-chol-
CC 5,22-dien-24-oyl-CoA + AH2; Xref=Rhea:RHEA:46320, ChEBI:CHEBI:13193,
CC ChEBI:CHEBI:17499, ChEBI:CHEBI:86018, ChEBI:CHEBI:86037;
CC Evidence={ECO:0000269|PubMed:25645564};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46321;
CC Evidence={ECO:0000269|PubMed:25645564};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000269|PubMed:25645564, ECO:0000269|PubMed:26161441};
CC Note=Binds 2 FAD per dimer. {ECO:0000269|PubMed:26161441};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=28 uM for 3-OCO-CoA (at pH 8.5 and 25 degrees Celsius)
CC {ECO:0000269|PubMed:26161441};
CC KM=2.5 uM for 3beta-hydroxy-chol-5-ene-24-oyl-CoA
CC {ECO:0000269|PubMed:25645564};
CC KM=47 uM for cholyl-CoA {ECO:0000269|PubMed:25645564};
CC KM=27 uM for deoxycholyl-CoA {ECO:0000269|PubMed:25645564};
CC Note=kcat is 5 sec(-1) for 3-OCO-CoA as substrate (at pH 8.5 and 25
CC degrees Celsius (PubMed:26161441). kcat is 3.7 sec(-1) with 3beta-
CC hydroxy-chol-5-ene-24-oyl-CoA as substrate. kcat is 0.22 sec(-1) with
CC cholyl-CoA as substrate. kcat is 0.44 sec(-1) with deoxycholyl-CoA as
CC substrate (PubMed:25645564). {ECO:0000269|PubMed:25645564,
CC ECO:0000269|PubMed:26161441};
CC -!- PATHWAY: Steroid metabolism; cholesterol degradation.
CC {ECO:0000305|PubMed:26161441}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:25645564,
CC ECO:0000269|PubMed:26161441}.
CC -!- INDUCTION: Induced by cholesterol and repressed by KstR.
CC {ECO:0000269|PubMed:17635188}.
CC -!- DOMAIN: Contains two ACAD domains separated by a short linker. The two
CC domains interact to form a single active site.
CC {ECO:0000269|PubMed:25645564}.
CC -!- SIMILARITY: Belongs to the acyl-CoA dehydrogenase family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; CP009480; AIR16364.1; -; Genomic_DNA.
DR EMBL; AL123456; CCP46396.1; -; Genomic_DNA.
DR RefSeq; NP_218090.1; NC_000962.3.
DR RefSeq; WP_003419394.1; NZ_NVQJ01000014.1.
DR AlphaFoldDB; P96855; -.
DR SMR; P96855; -.
DR STRING; 83332.Rv3573c; -.
DR SwissLipids; SLP:000001235; -.
DR PaxDb; P96855; -.
DR DNASU; 887843; -.
DR GeneID; 45427561; -.
DR GeneID; 887843; -.
DR KEGG; mtu:Rv3573c; -.
DR PATRIC; fig|83332.111.peg.3980; -.
DR TubercuList; Rv3573c; -.
DR eggNOG; COG1960; Bacteria.
DR HOGENOM; CLU_018204_9_3_11; -.
DR InParanoid; P96855; -.
DR OMA; DWAICLA; -.
DR PhylomeDB; P96855; -.
DR BioCyc; MetaCyc:G185E-7851-MON; -.
DR UniPathway; UPA01058; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro.
DR GO; GO:0016627; F:oxidoreductase activity, acting on the CH-CH group of donors; IEA:InterPro.
DR GO; GO:0006707; P:cholesterol catabolic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 1.10.540.10; -; 2.
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; 2.
DR Pfam; PF02770; Acyl-CoA_dh_M; 1.
DR Pfam; PF02771; Acyl-CoA_dh_N; 2.
DR SUPFAM; SSF47203; SSF47203; 2.
DR SUPFAM; SSF56645; SSF56645; 2.
PE 1: Evidence at protein level;
KW Cholesterol metabolism; FAD; Flavoprotein; Lipid degradation;
KW Lipid metabolism; Oxidoreductase; Reference proteome; Steroid metabolism;
KW Sterol metabolism; Virulence.
FT CHAIN 1..711
FT /note="Acyl-CoA dehydrogenase FadE34"
FT /id="PRO_0000438519"
FT MUTAGEN 236
FT /note="R->A: Displays less than 2% activity with cholyl-CoA
FT as substrate. Cannot bind FAD."
FT /evidence="ECO:0000269|PubMed:25645564"
FT MUTAGEN 581
FT /note="E->Q: Displays less than 1% activity with cholyl-CoA
FT as substrate. Still binds FAD."
FT /evidence="ECO:0000269|PubMed:25645564"
SQ SEQUENCE 711 AA; 74578 MW; 52B632900EFE196D CRC64;
MVATVTDEQS AARELVRGWA RTAASGAAAT AAVRDMEYGF EEGNADAWRP VFAGLAGLGL
FGVAVPEDCG GAGGSIEDLC AMVDEAARAL VPGPVATTAV ATLVVSDPKL RSALASGERF
AGVAIDGGVQ VDPKTSTASG TVGRVLGGAP GGVVLLPADG NWLLVDTACD EVVVEPLRAT
DFSLPLARMV LTSAPVTVLE VSGERVEDLA ATVLAAEAAG VARWTLDTAV AYAKVREQFG
KPIGSFQAVK HLCAQMLCRA EQADVAAADA ARAAADSDGT QLSIAAAVAA SIGIDAAKAN
AKDCIQVLGG IGCTWEHDAH LYLRRAHGIG GFLGGSGRWL RRVTALTQAG VRRRLGVDLA
EVAGLRPEIA AAVAEVAALP EEKRQVALAD TGLLAPHWPA PYGRGASPAE QLLIDQELAA
AKVERPDLVI GWWAAPTILE HGTPEQIERF VPATMRGEFL WCQLFSEPGA GSDLASLRTK
AVRADGGWLL TGQKVWTSAA HKARWGVCLA RTDPDAPKHK GITYFLVDMT TPGIEIRPLR
EITGDSLFNE VFLDNVFVPD EMVVGAVNDG WRLARTTLAN ERVAMATGTA LGNPMEELLK
VLGDMELDVA QQDRLGRLIL LAQAGALLDR RIAELAVGGQ DPGAQSSVRK LIGVRYRQAL
AEYLMEVSDG GGLVENRAVY DFLNTRCLTI AGGTEQILLT VAAERLLGLP R
