CHSE5_MYCTU
ID CHSE5_MYCTU Reviewed; 373 AA.
AC I6Y3Q0;
DT 30-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2012, sequence version 1.
DT 03-AUG-2022, entry version 73.
DE RecName: Full=Acyl-CoA dehydrogenase FadE27 {ECO:0000303|PubMed:26161441};
DE Short=ACAD {ECO:0000303|PubMed:26161441};
DE EC=1.3.99.- {ECO:0000305|PubMed:26161441};
DE AltName: Full=3-oxocholest-4-en-26-oyl-CoA dehydrogenase beta subunit {ECO:0000305|PubMed:26161441};
GN Name=fadE27; OrderedLocusNames=Rv3505;
GN ORFNames=LH57_19110 {ECO:0000312|EMBL:AIR16299.1};
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, PATHWAY, SUBSTRATE 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 (PubMed:26348625, PubMed:26161441).
CC {ECO:0000269|PubMed:26161441, 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; AIR16299.1; -; Genomic_DNA.
DR EMBL; AL123456; CCP46327.1; -; Genomic_DNA.
DR RefSeq; NP_218022.1; NC_000962.3.
DR RefSeq; WP_003419000.1; NZ_NVQJ01000042.1.
DR PDB; 4X28; X-ray; 1.99 A; C/D=1-373.
DR PDBsum; 4X28; -.
DR AlphaFoldDB; I6Y3Q0; -.
DR SMR; I6Y3Q0; -.
DR STRING; 83332.Rv3505; -.
DR PaxDb; I6Y3Q0; -.
DR PRIDE; I6Y3Q0; -.
DR DNASU; 888248; -.
DR GeneID; 888248; -.
DR KEGG; mtu:Rv3505; -.
DR PATRIC; fig|83332.111.peg.3903; -.
DR TubercuList; Rv3505; -.
DR eggNOG; COG1960; Bacteria.
DR HOGENOM; CLU_018204_5_3_11; -.
DR OMA; DIDHPVH; -.
DR PhylomeDB; I6Y3Q0; -.
DR BioCyc; MetaCyc:G185E-7782-MON; -.
DR UniPathway; UPA01058; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0003995; F:acyl-CoA dehydrogenase activity; IBA:GO_Central.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; 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; 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 3D-structure; Cholesterol metabolism; FAD; Flavoprotein; Lipid degradation;
KW Lipid metabolism; Oxidoreductase; Reference proteome; Steroid metabolism;
KW Sterol metabolism; Virulence.
FT CHAIN 1..373
FT /note="Acyl-CoA dehydrogenase FadE27"
FT /id="PRO_0000438521"
FT BINDING 251
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:26161441,
FT ECO:0007744|PDB:4X28"
FT BINDING 327
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:26161441,
FT ECO:0007744|PDB:4X28"
FT BINDING 331
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:26161441,
FT ECO:0007744|PDB:4X28"
FT HELIX 7..23
FT /evidence="ECO:0007829|PDB:4X28"
FT HELIX 26..33
FT /evidence="ECO:0007829|PDB:4X28"
FT STRAND 35..37
FT /evidence="ECO:0007829|PDB:4X28"
FT HELIX 41..49
FT /evidence="ECO:0007829|PDB:4X28"
FT HELIX 52..55
FT /evidence="ECO:0007829|PDB:4X28"
FT HELIX 59..61
FT /evidence="ECO:0007829|PDB:4X28"
FT HELIX 68..80
FT /evidence="ECO:0007829|PDB:4X28"
FT HELIX 87..90
FT /evidence="ECO:0007829|PDB:4X28"
FT TURN 91..93
FT /evidence="ECO:0007829|PDB:4X28"
FT HELIX 94..101
FT /evidence="ECO:0007829|PDB:4X28"
FT HELIX 104..108
FT /evidence="ECO:0007829|PDB:4X28"
FT HELIX 110..115
FT /evidence="ECO:0007829|PDB:4X28"
FT STRAND 121..123
FT /evidence="ECO:0007829|PDB:4X28"
FT STRAND 135..138
FT /evidence="ECO:0007829|PDB:4X28"
FT STRAND 140..153
FT /evidence="ECO:0007829|PDB:4X28"
FT HELIX 155..157
FT /evidence="ECO:0007829|PDB:4X28"
FT STRAND 159..167
FT /evidence="ECO:0007829|PDB:4X28"
FT STRAND 170..177
FT /evidence="ECO:0007829|PDB:4X28"
FT STRAND 183..187
FT /evidence="ECO:0007829|PDB:4X28"
FT STRAND 196..207
FT /evidence="ECO:0007829|PDB:4X28"
FT HELIX 208..210
FT /evidence="ECO:0007829|PDB:4X28"
FT STRAND 211..214
FT /evidence="ECO:0007829|PDB:4X28"
FT HELIX 215..250
FT /evidence="ECO:0007829|PDB:4X28"
FT HELIX 258..260
FT /evidence="ECO:0007829|PDB:4X28"
FT HELIX 262..291
FT /evidence="ECO:0007829|PDB:4X28"
FT HELIX 304..329
FT /evidence="ECO:0007829|PDB:4X28"
FT HELIX 330..333
FT /evidence="ECO:0007829|PDB:4X28"
FT HELIX 340..353
FT /evidence="ECO:0007829|PDB:4X28"
FT HELIX 356..370
FT /evidence="ECO:0007829|PDB:4X28"
SQ SEQUENCE 373 AA; 39008 MW; 0C2C405B45D46F88 CRC64;
MDFTTTEAAQ DLGGLVDTIV DAVCTPEHQR ELDKLEQRFD RELWRKLIDA GILSSAAPES
LGGDGFGVLE QVAVLVALGH QLAAVPYLES VVLAAGALAR FGSPELQQGW GVSAVSGDRI
LTVALDGEMG EGPVQAAGTG HGYRLTGTRT QVGYGPVADA FLVPAETDSG AAVFLVAAGD
PGVAVTALAT TGLGSVGHLE LNGAKVDAAR RVGGTDVAVW LGTLSTLSRT AFQLGVLERG
LQMTAEYART REQFDRPIGS FQAVGQRLAD GYIDVKGLRL TLTQAAWRVA EDSLASRECP
QPADIDVATA GFWAAEAGHR VAHTIVHVHG GVGVDTDHPV HRYFLAAKQT EFALGGATGQ
LRRIGRELAE TPA
