CHSE4_MYCTU
ID CHSE4_MYCTU Reviewed; 400 AA.
AC I6YCA3;
DT 30-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2012, sequence version 1.
DT 03-AUG-2022, entry version 75.
DE RecName: Full=Acyl-CoA dehydrogenase FadE26 {ECO:0000303|PubMed:26161441};
DE Short=ACAD {ECO:0000303|PubMed:26161441};
DE EC=1.3.99.- {ECO:0000269|PubMed:26161441};
DE AltName: Full=3-oxocholest-4-en-26-oyl-CoA dehydrogenase alpha subunit {ECO:0000305|PubMed:26161441};
GN Name=fadE26; OrderedLocusNames=Rv3504;
GN ORFNames=LH57_19105 {ECO:0000312|EMBL:AIR16298.1};
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, AND SUBSTRATE SPECIFICITY.
RX PubMed=26348625; DOI=10.1021/acs.biochem.5b00911;
RA Lu R., Schmitz W., Sampson N.S.;
RT "Alpha-methyl acyl CoA racemase provides Mycobacterium tuberculosis
RT catabolic access to cholesterol esters.";
RL Biochemistry 54:5669-5672(2015).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (1.99 ANGSTROMS) IN COMPLEX WITH FAD, FUNCTION,
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR, ACTIVITY
RP REGULATION, ACTIVE SITE, MUTAGENESIS OF GLU-247, PATHWAY, SUBSTRATE
RP SPECIFICITY, 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 first cycle of side chain dehydrogenation in
CC the beta-oxidation of cholesterol catabolism (PubMed:26161441). It
CC contributes partly to the virulence by increasing the efficiency of
CC beta-oxidation. Catalyzes the dehydrogenation of acyl-CoA ester side
CC chains of (25S)-3-oxo-cholest-4-en-26-oyl-CoA (3-OCS-CoA) to yield
CC (24E)-3-oxo-cholest-4,24-dien-26-oyl-CoA (PubMed:26348625,
CC PubMed:26161441). Also able to dehydrogenate steroyl-CoA such as 3-oxo-
CC chol-4-en-24-oyl-CoA (3-OCO-CoA) as well as 3-oxo-4-pregnene-20-
CC carboxyl-CoA (3-OPC-CoA) (PubMed:26161441). It dehydrogenates only
CC (25S)-OCS-CoA diastereomer (Probable). {ECO:0000269|PubMed:26161441,
CC ECO:0000269|PubMed:26348625}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(25S)-3-oxocholest-4-en-26-oyl-CoA + A = 3-oxo-cholest-4,24-
CC dien-26-oyl-CoA + AH2; Xref=Rhea:RHEA:46688, ChEBI:CHEBI:13193,
CC ChEBI:CHEBI:17499, ChEBI:CHEBI:83819, ChEBI:CHEBI:86414;
CC Evidence={ECO:0000269|PubMed:26161441};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000269|PubMed:26161441};
CC Note=Binds 1 FAD per heterodimer. {ECO:0000269|PubMed:26161441};
CC -!- ACTIVITY REGULATION: Uncompetitively inhibited by high concentration of
CC 3-OCS-CoA. {ECO:0000269|PubMed:26161441}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=2.6 uM for 3-OCO-CoA (at pH 8.5 and 25 degrees Celsius)
CC {ECO:0000269|PubMed:26161441};
CC KM=3.3 uM for 3-OPC-CoA (at pH 8.5 and 25 degrees Celsius)
CC {ECO:0000269|PubMed:26161441};
CC KM=3.4 uM for 3-OCS-CoA (at pH 8.5 and 25 degrees Celsius)
CC {ECO:0000269|PubMed:26161441};
CC KM=4.1 uM for octanoyl-CoA (at pH 8.5 and 25 degrees Celsius)
CC {ECO:0000269|PubMed:26161441};
CC Note=kcat is 2.7 sec(-1) for 3-OCS-CoA as substrate (at pH 8.5 and 25
CC degrees Celsius). kcat is 1.5 sec(-1) for 3-OPC-CoA as substrate (at
CC pH 8.5 and 25 degrees Celsius). kcat is 0.48 sec(-1) for 3-OCO-CoA as
CC substrate (at pH 8.5 and 25 degrees Celsius). kcat is 0.042 sec(-1)
CC for octanoyl-CoA as substrate (at pH 8.5 and 25 degrees Celsius).
CC {ECO:0000269|PubMed:26161441};
CC -!- PATHWAY: Steroid metabolism; cholesterol degradation.
CC {ECO:0000305|PubMed:26161441}.
CC -!- SUBUNIT: Heterotetramer (dimer of heterodimers) composed of FadE26 and
CC FadE27. {ECO:0000269|PubMed:26161441}.
CC -!- INDUCTION: Induced by cholesterol and repressed by KstR.
CC {ECO:0000269|PubMed:17635188}.
CC -!- SIMILARITY: Belongs to the acyl-CoA dehydrogenase family.
CC {ECO:0000305}.
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DR EMBL; CP009480; AIR16298.1; -; Genomic_DNA.
DR EMBL; AL123456; CCP46326.1; -; Genomic_DNA.
DR RefSeq; NP_218021.1; NC_000962.3.
DR RefSeq; WP_003418997.1; NZ_NVQJ01000042.1.
DR PDB; 4X28; X-ray; 1.99 A; A/B=1-400.
DR PDBsum; 4X28; -.
DR AlphaFoldDB; I6YCA3; -.
DR SMR; I6YCA3; -.
DR STRING; 83332.Rv3504; -.
DR PaxDb; I6YCA3; -.
DR PRIDE; I6YCA3; -.
DR DNASU; 887722; -.
DR GeneID; 887722; -.
DR KEGG; mtu:Rv3504; -.
DR PATRIC; fig|83332.111.peg.3902; -.
DR TubercuList; Rv3504; -.
DR eggNOG; COG1960; Bacteria.
DR HOGENOM; CLU_018204_9_0_11; -.
DR OMA; APTIMHF; -.
DR PhylomeDB; I6YCA3; -.
DR BioCyc; MetaCyc:G185E-7781-MON; -.
DR UniPathway; UPA01058; -.
DR Proteomes; UP000001584; Chromosome.
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; -; 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 3D-structure; Cholesterol metabolism; FAD; Flavoprotein; Lipid degradation;
KW Lipid metabolism; Oxidoreductase; Reference proteome; Steroid metabolism;
KW Sterol metabolism; Virulence.
FT CHAIN 1..400
FT /note="Acyl-CoA dehydrogenase FadE26"
FT /id="PRO_0000438520"
FT ACT_SITE 247
FT /note="Proton acceptor"
FT /evidence="ECO:0000305|PubMed:26161441"
FT BINDING 127..130
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:26161441,
FT ECO:0007744|PDB:4X28"
FT BINDING 136
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:26161441,
FT ECO:0007744|PDB:4X28"
FT BINDING 162
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:26161441,
FT ECO:0007744|PDB:4X28"
FT BINDING 380..382
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:26161441,
FT ECO:0007744|PDB:4X28"
FT MUTAGEN 247
FT /note="E->A: Loss of dehydrogenase activity."
FT /evidence="ECO:0000269|PubMed:26161441"
FT HELIX 7..23
FT /evidence="ECO:0007829|PDB:4X28"
FT HELIX 26..32
FT /evidence="ECO:0007829|PDB:4X28"
FT HELIX 44..54
FT /evidence="ECO:0007829|PDB:4X28"
FT TURN 58..61
FT /evidence="ECO:0007829|PDB:4X28"
FT HELIX 64..66
FT /evidence="ECO:0007829|PDB:4X28"
FT HELIX 73..86
FT /evidence="ECO:0007829|PDB:4X28"
FT HELIX 92..96
FT /evidence="ECO:0007829|PDB:4X28"
FT HELIX 98..105
FT /evidence="ECO:0007829|PDB:4X28"
FT HELIX 108..119
FT /evidence="ECO:0007829|PDB:4X28"
FT STRAND 125..128
FT /evidence="ECO:0007829|PDB:4X28"
FT STRAND 134..136
FT /evidence="ECO:0007829|PDB:4X28"
FT HELIX 138..140
FT /evidence="ECO:0007829|PDB:4X28"
FT STRAND 144..148
FT /evidence="ECO:0007829|PDB:4X28"
FT STRAND 151..159
FT /evidence="ECO:0007829|PDB:4X28"
FT HELIX 164..166
FT /evidence="ECO:0007829|PDB:4X28"
FT STRAND 168..176
FT /evidence="ECO:0007829|PDB:4X28"
FT HELIX 178..180
FT /evidence="ECO:0007829|PDB:4X28"
FT HELIX 184..186
FT /evidence="ECO:0007829|PDB:4X28"
FT STRAND 189..195
FT /evidence="ECO:0007829|PDB:4X28"
FT STRAND 201..206
FT /evidence="ECO:0007829|PDB:4X28"
FT STRAND 208..211
FT /evidence="ECO:0007829|PDB:4X28"
FT STRAND 214..225
FT /evidence="ECO:0007829|PDB:4X28"
FT HELIX 226..228
FT /evidence="ECO:0007829|PDB:4X28"
FT STRAND 229..232
FT /evidence="ECO:0007829|PDB:4X28"
FT HELIX 237..240
FT /evidence="ECO:0007829|PDB:4X28"
FT TURN 241..244
FT /evidence="ECO:0007829|PDB:4X28"
FT HELIX 255..269
FT /evidence="ECO:0007829|PDB:4X28"
FT HELIX 279..281
FT /evidence="ECO:0007829|PDB:4X28"
FT HELIX 283..308
FT /evidence="ECO:0007829|PDB:4X28"
FT HELIX 320..345
FT /evidence="ECO:0007829|PDB:4X28"
FT HELIX 346..348
FT /evidence="ECO:0007829|PDB:4X28"
FT HELIX 360..362
FT /evidence="ECO:0007829|PDB:4X28"
FT HELIX 363..370
FT /evidence="ECO:0007829|PDB:4X28"
FT HELIX 372..376
FT /evidence="ECO:0007829|PDB:4X28"
FT STRAND 377..379
FT /evidence="ECO:0007829|PDB:4X28"
FT HELIX 381..393
FT /evidence="ECO:0007829|PDB:4X28"
SQ SEQUENCE 400 AA; 43785 MW; 2B25B8A76861F271 CRC64;
MRISYTPQQE ELRRELRSYF ATLMTPERRE ALSSVQGEYG VGNVYRETIA QMGRDGWLAL
GWPKEYGGQG RSAMDQLIFT DEAAIAGAPV PFLTINSVAP TIMAYGTDEQ KRFFLPRIAA
GDLHFSIGYS EPGAGTDLAN LRTTAVRDGD DYVVNGQKMW TSLIQYADYV WLAVRTNPES
SGAKKHRGIS VLIVPTTAEG FSWTPVHTMA GPDTSATYYS DVRVPVANRV GEENAGWKLV
TNQLNHERVA LVSPAPIFGC LREVREWAQN TKDAGGTRLI DSEWVQLNLA RVHAKAEVLK
LINWELASSQ SGPKDAGPSP ADASAAKVFG TELATEAYRL LMEVLGTAAT LRQNSPGALL
RGRVERMHRA CLILTFGGGT NEVQRDIIGM VALGLPRANR
