DESA3_MYCTU
ID DESA3_MYCTU Reviewed; 427 AA.
AC P9WNZ3; L0TC73; Q6MWZ3; Q7D5W1;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 43.
DE RecName: Full=NADPH-dependent stearoyl-CoA 9-desaturase {ECO:0000305};
DE EC=1.14.19.n4 {ECO:0000269|PubMed:17087501};
DE AltName: Full=Delta(9)-stearoyl desaturase {ECO:0000303|PubMed:14559907};
DE AltName: Full=Stearoyl-CoA 9-desaturase (NADPH) {ECO:0000305};
DE AltName: Full=Stearoyl-CoA Delta(9)-desaturase {ECO:0000303|PubMed:14559907};
GN Name=desA3 {ECO:0000303|PubMed:14559907}; OrderedLocusNames=Rv3229c;
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 FUNCTION, ACTIVITY REGULATION, DRUG TARGET, INDUCTION, PATHWAY, AND
RP SUBCELLULAR LOCATION.
RC STRAIN=H37Rv;
RX PubMed=14559907; DOI=10.1074/jbc.m311209200;
RA Phetsuksiri B., Jackson M., Scherman H., McNeil M., Besra G.S.,
RA Baulard A.R., Slayden R.A., DeBarber A.E., Barry C.E. III, Baird M.S.,
RA Crick D.C., Brennan P.J.;
RT "Unique mechanism of action of the thiourea drug isoxyl on Mycobacterium
RT tuberculosis.";
RL J. Biol. Chem. 278:53123-53130(2003).
RN [3]
RP DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=14569030; DOI=10.1073/pnas.2134250100;
RA Sassetti C.M., Rubin E.J.;
RT "Genetic requirements for mycobacterial survival during infection.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:12989-12994(2003).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND INTERACTION WITH
RP RV3230C.
RC STRAIN=H37Rv;
RX PubMed=17087501; DOI=10.1021/bi0615285;
RA Chang Y., Fox B.G.;
RT "Identification of Rv3230c as the NADPH oxidoreductase of a two-protein
RT DesA3 acyl-CoA desaturase in Mycobacterium tuberculosis H37Rv.";
RL Biochemistry 45:13476-13486(2006).
RN [5]
RP IDENTIFICATION AS A DRUG TARGET [LARGE SCALE ANALYSIS].
RX PubMed=19099550; DOI=10.1186/1752-0509-2-109;
RA Raman K., Yeturu K., Chandra N.;
RT "targetTB: a target identification pipeline for Mycobacterium tuberculosis
RT through an interactome, reactome and genome-scale structural analysis.";
RL BMC Syst. Biol. 2:109-109(2008).
RN [6]
RP DEGRADATION BY PROTEOLYSIS, AND MUTAGENESIS OF 425-LEU--ALA-427.
RC STRAIN=H37Rv;
RX PubMed=18723625; DOI=10.1128/jb.00585-08;
RA Chang Y., Wesenberg G.E., Bingman C.A., Fox B.G.;
RT "In vivo inactivation of the mycobacterial integral membrane stearoyl
RT coenzyme A desaturase DesA3 by a C-terminus-specific degradation process.";
RL J. Bacteriol. 190:6686-6696(2008).
RN [7]
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).
CC -!- FUNCTION: Is likely involved in the aerobic desaturation system
CC responsible for the synthesis of oleic acid from stearoyl-CoA; oleic
CC acid is a precursor of mycobacterial membrane phospholipids and
CC triglycerides. Catalyzes the conversion of stearoyl-CoA to oleoyl-CoA
CC by introduction of a cis double bond between carbons 9 and 10 of the
CC acyl chain. Requires the electron transfer partner Rv3230c to pass two
CC electrons from NADPH to its active site diiron center. Is also able to
CC catalyze the 9-desaturation of palmitoyl-CoA to palmitoleoyl-CoA.
CC {ECO:0000269|PubMed:14559907, ECO:0000269|PubMed:17087501}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + NADPH + O2 + octadecanoyl-CoA = (9Z)-octadecenoyl-CoA +
CC 2 H2O + NADP(+); Xref=Rhea:RHEA:37971, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57387,
CC ChEBI:CHEBI:57394, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC EC=1.14.19.n4; Evidence={ECO:0000269|PubMed:17087501};
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000250|UniProtKB:P13516};
CC Note=Expected to bind 2 Fe(2+) ions per subunit.
CC {ECO:0000250|UniProtKB:P13516};
CC -!- ACTIVITY REGULATION: Inhibited by the anti-tuberculosis drug isoxyl
CC (ISO). {ECO:0000269|PubMed:14559907}.
CC -!- PATHWAY: Lipid metabolism; fatty acid metabolism.
CC {ECO:0000269|PubMed:14559907}.
CC -!- SUBUNIT: Interacts with the electron transfer protein Rv3230c to form a
CC functional acyl-CoA desaturase complex. {ECO:0000269|PubMed:17087501}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:14559907,
CC ECO:0000269|PubMed:17087501}; Multi-pass membrane protein
CC {ECO:0000305|PubMed:17087501}.
CC -!- INDUCTION: Is expressed during the exponential growth.
CC {ECO:0000269|PubMed:14559907}.
CC -!- PTM: Is rapidly degraded by a mycobacterial protein degradation system
CC that specifically targets the residues LAA at the C-terminus, leading
CC to a post-translational proteolytic regulation of DesA3 essential
CC activity. {ECO:0000269|PubMed:18723625}.
CC -!- DISRUPTION PHENOTYPE: Strains lacking this gene are shown to be
CC attenuated in a mouse tuberculosis model.
CC {ECO:0000269|PubMed:14569030}.
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC {ECO:0000305|PubMed:19099550}.
CC -!- SIMILARITY: Belongs to the fatty acid desaturase type 1 family.
CC {ECO:0000305}.
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DR EMBL; AL123456; CCP46048.1; -; Genomic_DNA.
DR PIR; G70590; G70590.
DR RefSeq; WP_003416919.1; NZ_NVQJ01000003.1.
DR RefSeq; YP_177948.1; NC_000962.3.
DR AlphaFoldDB; P9WNZ3; -.
DR STRING; 83332.Rv3229c; -.
DR SwissLipids; SLP:000001156; -.
DR PaxDb; P9WNZ3; -.
DR DNASU; 888821; -.
DR GeneID; 888821; -.
DR KEGG; mtu:Rv3229c; -.
DR TubercuList; Rv3229c; -.
DR eggNOG; COG3239; Bacteria.
DR OMA; HQVEHHI; -.
DR PhylomeDB; P9WNZ3; -.
DR BioCyc; MetaCyc:G185E-7503-MON; -.
DR UniPathway; UPA00199; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0016213; F:linoleoyl-CoA desaturase activity; IDA:MTBBASE.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0016717; F:oxidoreductase activity, acting on paired donors, with oxidation of a pair of donors resulting in the reduction of molecular oxygen to two molecules of water; IBA:GO_Central.
DR GO; GO:0006629; P:lipid metabolic process; IBA:GO_Central.
DR GO; GO:0042759; P:long-chain fatty acid biosynthetic process; IDA:MTBBASE.
DR InterPro; IPR005804; FA_desaturase_dom.
DR InterPro; IPR012171; Fatty_acid_desaturase.
DR PANTHER; PTHR19353; PTHR19353; 1.
DR Pfam; PF00487; FA_desaturase; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Fatty acid biosynthesis; Fatty acid metabolism; Iron;
KW Lipid biosynthesis; Lipid metabolism; Membrane; Metal-binding; NADP;
KW Oxidoreductase; Reference proteome.
FT CHAIN 1..427
FT /note="NADPH-dependent stearoyl-CoA 9-desaturase"
FT /id="PRO_0000392677"
FT BINDING 90
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P13516,
FT ECO:0000305|PubMed:14559907"
FT BINDING 94
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P13516,
FT ECO:0000305|PubMed:14559907"
FT BINDING 125
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P13516,
FT ECO:0000305|PubMed:14559907"
FT BINDING 129
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P13516,
FT ECO:0000305|PubMed:14559907"
FT BINDING 130
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P13516,
FT ECO:0000305|PubMed:14559907"
FT BINDING 304
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P13516,
FT ECO:0000305|PubMed:14559907"
FT BINDING 308
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P13516,
FT ECO:0000305|PubMed:14559907"
FT BINDING 309
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P13516,
FT ECO:0000305|PubMed:14559907"
FT MUTAGEN 425..427
FT /note="LAA->DKD,LEA: Enhances catalytic activity and
FT stability."
FT /evidence="ECO:0000269|PubMed:18723625"
SQ SEQUENCE 427 AA; 48443 MW; 56341F7F1B393A65 CRC64;
MAITDVDVFA HLTDADIENL AAELDAIRRD VEESRGERDA RYIRRTIAAQ RALEVSGRLL
LAGSSRRLAW WTGALTLGVA KIIENMEIGH NVMHGQWDWM NDPEIHSSTW EWDMSGSSKH
WRYTHNFVHH KYTNILGMDD DVGYGMLRVT RDQRWKRYNI FNVVWNTILA IGFEWGVALQ
HLEIGKIFKG RADREAAKTR LREFSAKAGR QVFKDYVAFP ALTSLSPGAT YRSTLTANVV
ANVIRNVWSN AVIFCGHFPD GAEKFTKTDM IGEPKGQWYL RQMLGSANFN AGPALRFMSG
NLCHQIEHHL YPDLPSNRLH EISVRVREVC DRYDLPYTTG SFLVQYGKTW RTLAKLSLPD
KYLRDNADDA PETRSERMFA GLGPGFAGAD PVTGRRRGLK TAIAAVRGRR RSKRMAKSVT
EPDDLAA
