KASA_MYCTU
ID KASA_MYCTU Reviewed; 416 AA.
AC P9WQD9; L0T991; P63454; Q10524;
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=3-oxoacyl-[acyl-carrier-protein] synthase 1;
DE EC=2.3.1.293 {ECO:0000305|PubMed:11600501, ECO:0000305|PubMed:12464486, ECO:0000305|PubMed:24108128};
DE AltName: Full=Beta-ketoacyl-ACP synthase 1;
DE Short=KAS 1;
DE AltName: Full=Beta-ketoacyl-acyl carrier protein synthase KasA {ECO:0000303|PubMed:11600501};
DE AltName: Full=Meromycolic acid 3-oxoacyl-(acyl carrier protein) synthase I;
GN Name=kasA {ECO:0000303|PubMed:10747933}; OrderedLocusNames=Rv2245;
GN ORFNames=MTCY427.26;
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 IDENTIFICATION AS A DRUG TARGET.
RX PubMed=10747933; DOI=10.1074/jbc.m000569200;
RA Kremer L., Douglas J.D., Baulard A.R., Morehouse C., Guy M.R., Alland D.,
RA Dover L.G., Lakey J.H., Jacobs W.R. Jr., Brennan P.J., Minnikin D.E.,
RA Besra G.S.;
RT "Thiolactomycin and related analogues as novel anti-mycobacterial agents
RT targeting KasA and KasB condensing enzymes in Mycobacterium tuberculosis.";
RL J. Biol. Chem. 275:16857-16864(2000).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND PATHWAY.
RX PubMed=11600501; DOI=10.1074/jbc.m108903200;
RA Schaeffer M.L., Agnihotri G., Volker C., Kallender H., Brennan P.J.,
RA Lonsdale J.T.;
RT "Purification and biochemical characterization of the Mycobacterium
RT tuberculosis beta-ketoacyl-acyl carrier protein synthases KasA and KasB.";
RL J. Biol. Chem. 276:47029-47037(2001).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, IDENTIFICATION AS A DRUG TARGET, AND
RP MUTAGENESIS OF CYS-171; HIS-311; LYS-340 AND HIS-345.
RX PubMed=12023885; DOI=10.1042/bj20011628;
RA Kremer L., Dover L.G., Carrere S., Nampoothiri K.M., Lesjean S.,
RA Brown A.K., Brennan P.J., Minnikin D.E., Locht C., Besra G.S.;
RT "Mycolic acid biosynthesis and enzymic characterization of the beta-
RT ketoacyl-ACP synthase A-condensing enzyme from Mycobacterium
RT tuberculosis.";
RL Biochem. J. 364:423-430(2002).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND MUTAGENESIS OF ASP-66; GLY-269;
RP GLY-312 AND PHE-413.
RX PubMed=12464486; DOI=10.1054/tube.2002.0333;
RA Slayden R.A., Barry C.E. III;
RT "The role of KasA and KasB in the biosynthesis of meromycolic acids and
RT isoniazid resistance in Mycobacterium tuberculosis.";
RL Tuberculosis 82:149-160(2002).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES,
RP PHOSPHORYLATION, AND ACTIVITY REGULATION.
RX PubMed=16873379; DOI=10.1074/jbc.m601691200;
RA Molle V., Brown A.K., Besra G.S., Cozzone A.J., Kremer L.;
RT "The condensing activities of the Mycobacterium tuberculosis type II fatty
RT acid synthase are differentially regulated by phosphorylation.";
RL J. Biol. Chem. 281:30094-30103(2006).
RN [7]
RP PATHWAY.
RX PubMed=19604470; DOI=10.1016/j.str.2009.06.006;
RA Swanson S., Gokulan K., Sacchettini J.C.;
RT "KasA, another brick in the mycobacterial cell wall.";
RL Structure 17:914-915(2009).
RN [8]
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 [9]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=22017312; DOI=10.1021/bi201199x;
RA Borgaro J.G., Chang A., Machutta C.A., Zhang X., Tonge P.J.;
RT "Substrate recognition by beta-ketoacyl-ACP synthases.";
RL Biochemistry 50:10678-10686(2011).
RN [10]
RP IDENTIFICATION AS A DRUG TARGET, AND MOLECULAR DYNAMICS SIMULATIONS.
RX PubMed=22076471; DOI=10.1007/s10822-011-9483-4;
RA Schaefer B., Kisker C., Sotriffer C.A.;
RT "Molecular dynamics of Mycobacterium tuberculosis KasA: implications for
RT inhibitor and substrate binding and consequences for drug design.";
RL J. Comput. Aided Mol. Des. 25:1053-1069(2011).
RN [11]
RP REACTION MECHANISM, DOMAIN, AND ACTIVE SITE.
RX PubMed=24479625; DOI=10.1021/bi401308j;
RA Lee W., Engels B.;
RT "The protonation state of catalytic residues in the resting state of KasA
RT revisited: detailed mechanism for the activation of KasA by its own
RT substrate.";
RL Biochemistry 53:919-931(2014).
RN [12] {ECO:0007744|PDB:2WGD, ECO:0007744|PDB:2WGE, ECO:0007744|PDB:2WGF, ECO:0007744|PDB:2WGG}
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF MUTANT GLN-171 AND OF WILD-TYPE
RP IN COMPLEX WITH THIOLACTOMYCIN INHIBITOR, MUTAGENESIS OF CYS-171, AND
RP SUBUNIT.
RX PubMed=19604480; DOI=10.1016/j.str.2009.04.012;
RA Luckner S.R., Machutta C.A., Tonge P.J., Kisker C.;
RT "Crystal structures of Mycobacterium tuberculosis KasA show mode of action
RT within cell wall biosynthesis and its inhibition by thiolactomycin.";
RL Structure 17:1004-1013(2009).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF WILD-TYPE AND MUTANT GLN-171 IN
RP COMPLEXES WITH SUBSTRATE ANALOGS, FUNCTION, CATALYTIC ACTIVITY, REACTION
RP MECHANISM, AND ACTIVE SITE.
RX PubMed=24108128; DOI=10.1074/jbc.m113.511436;
RA Schiebel J., Kapilashrami K., Fekete A., Bommineni G.R., Schaefer C.M.,
RA Mueller M.J., Tonge P.J., Kisker C.;
RT "Structural basis for the recognition of mycolic acid precursors by KasA, a
RT condensing enzyme and drug target from Mycobacterium tuberculosis.";
RL J. Biol. Chem. 288:34190-34204(2013).
RN [14] {ECO:0007744|PDB:5LD8}
RP X-RAY CRYSTALLOGRAPHY (2.13 ANGSTROMS) OF 2-416 IN COMPLEX WITH GSK3011724A
RP INHIBITOR, AND DRUG TARGET.
RX PubMed=27581223; DOI=10.1038/ncomms12581;
RA Abrahams K.A., Chung C.W., Ghidelli-Disse S., Rullas J.,
RA Rebollo-Lopez M.J., Gurcha S.S., Cox J.A., Mendoza A., Jimenez-Navarro E.,
RA Martinez-Martinez M.S., Neu M., Shillings A., Homes P., Argyrou A.,
RA Casanueva R., Loman N.J., Moynihan P.J., Lelievre J., Selenski C.,
RA Axtman M., Kremer L., Bantscheff M., Angulo-Barturen I., Izquierdo M.C.,
RA Cammack N.C., Drewes G., Ballell L., Barros D., Besra G.S., Bates R.H.;
RT "Identification of KasA as the cellular target of an anti-tubercular
RT scaffold.";
RL Nat. Commun. 7:12581-12581(2016).
RN [15] {ECO:0007744|PDB:6Y2I, ECO:0007744|PDB:6Y2J}
RP X-RAY CRYSTALLOGRAPHY (1.53 ANGSTROMS) OF 2-416 IN COMPLEXES WITH
RP INHIBITORS, AND DRUG TARGET.
RX PubMed=32196311; DOI=10.1021/acsinfecdis.9b00493;
RA Cunningham F., Esquivias J., Fernandez-Menendez R., Perez A., Guardia A.,
RA Escribano J., Rivero C., Vimal M., Cacho M., de Dios-Anton P.,
RA Martinez-Martinez M.S., Jimenez E., Huertas Valentin L.,
RA Rebollo-Lopez M.J., Lopez-Roman E.M., Sousa-Morcuende V., Rullas J.,
RA Neu M., Chung C.W., Bates R.H.;
RT "Exploring the SAR of the beta-ketoacyl-ACP synthase inhibitor GSK3011724A
RT and optimization around a genotoxic metabolite.";
RL ACS Infect. Dis. 6:1098-1109(2020).
RN [16] {ECO:0007744|PDB:6P9K, ECO:0007744|PDB:6P9L, ECO:0007744|PDB:6P9M}
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 3-416 IN COMPLEXES WITH
RP INHIBITORS, AND DRUG TARGET.
RX PubMed=32197094; DOI=10.1016/j.chembiol.2020.02.007;
RA Inoyama D., Awasthi D., Capodagli G.C., Tsotetsi K., Sukheja P.,
RA Zimmerman M., Li S.G., Jadhav R., Russo R., Wang X., Grady C., Richmann T.,
RA Shrestha R., Li L., Ahn Y.M., Ho Liang H.P., Mina M., Park S., Perlin D.S.,
RA Connell N., Dartois V., Alland D., Neiditch M.B., Kumar P.,
RA Freundlich J.S.;
RT "A preclinical candidate targeting Mycobacterium tuberculosis KasA.";
RL Cell Chem. Biol. 27:560-570.e10(2020).
CC -!- FUNCTION: Part of the mycobacterial fatty acid elongation system FAS-
CC II, which is involved in mycolic acid biosynthesis. Catalyzes the
CC elongation of long chain acyl-ACP substrates by the addition of two
CC carbons from malonyl-ACP to an acyl acceptor (PubMed:11600501,
CC PubMed:12023885, PubMed:12464486, PubMed:16873379, PubMed:22017312,
CC PubMed:24108128). Involved in the initial extension of the mycolate
CC chain and forms monounsaturated fatty acids that averaged 40 carbons in
CC length (PubMed:12464486). {ECO:0000269|PubMed:11600501,
CC ECO:0000269|PubMed:12023885, ECO:0000269|PubMed:12464486,
CC ECO:0000269|PubMed:16873379, ECO:0000269|PubMed:22017312,
CC ECO:0000269|PubMed:24108128}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an ultra-long-chain mono-unsaturated fatty acyl-[ACP] + H(+) +
CC malonyl-[ACP] = a 3-oxo-ultra-long-chain mono-unsaturated fatty acyl-
CC [ACP] + CO2 + holo-[ACP]; Xref=Rhea:RHEA:65312, Rhea:RHEA-COMP:9623,
CC Rhea:RHEA-COMP:9685, Rhea:RHEA-COMP:16765, Rhea:RHEA-COMP:16775,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:64479,
CC ChEBI:CHEBI:78449, ChEBI:CHEBI:156399, ChEBI:CHEBI:156400;
CC EC=2.3.1.293; Evidence={ECO:0000305|PubMed:11600501,
CC ECO:0000305|PubMed:12464486, ECO:0000305|PubMed:24108128};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65313;
CC Evidence={ECO:0000305|PubMed:11600501, ECO:0000305|PubMed:12464486,
CC ECO:0000305|PubMed:24108128};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + hexadecanoyl-[ACP] + malonyl-[ACP] = 3-oxooctadecanoyl-
CC [ACP] + CO2 + holo-[ACP]; Xref=Rhea:RHEA:41916, Rhea:RHEA-COMP:9623,
CC Rhea:RHEA-COMP:9652, Rhea:RHEA-COMP:9653, Rhea:RHEA-COMP:9685,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:64479,
CC ChEBI:CHEBI:78449, ChEBI:CHEBI:78483, ChEBI:CHEBI:78487;
CC Evidence={ECO:0000269|PubMed:11600501, ECO:0000269|PubMed:12023885,
CC ECO:0000269|PubMed:16873379, ECO:0000269|PubMed:22017312};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41917;
CC Evidence={ECO:0000269|PubMed:11600501, ECO:0000269|PubMed:12023885,
CC ECO:0000269|PubMed:16873379, ECO:0000269|PubMed:22017312};
CC -!- ACTIVITY REGULATION: Phosphorylation decreases the condensation
CC activity. {ECO:0000269|PubMed:16873379}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=3.2 uM for hexadecanoyl-[ACP] {ECO:0000269|PubMed:11600501};
CC KM=18.7 uM for hexadecanoyl-[ACP] {ECO:0000269|PubMed:16873379};
CC KM=2.5 uM for eicosanoyl-[ACP] {ECO:0000269|PubMed:11600501};
CC KM=13.5 uM for malonyl-[ACP] {ECO:0000269|PubMed:11600501};
CC KM=11.8 uM for malonyl-[ACP] {ECO:0000269|PubMed:16873379};
CC KM=5.8 uM for malonyl-AcpM (in the presence of hexadecanoyl-AcpM)
CC {ECO:0000269|PubMed:22017312};
CC KM=0.4 uM for hexadecanoyl-CoA (in the presence of malonyl-AcpM)
CC {ECO:0000269|PubMed:22017312};
CC KM=9.0 uM for malonyl-CoA (in the presence of hexadecanoyl-AcpM)
CC {ECO:0000269|PubMed:22017312};
CC Note=kcat is 5.3 min(-1) with hexadecanoyl-[ACP] as substrate. kcat
CC is 4.5 min(-1) with eicosanoyl-[ACP] as substrate. kcat is 4.8 min(-
CC 1) with malonyl-[ACP] as substrate (PubMed:11600501). kcat is 21
CC min(-1) with malonyl-CoA as substrate. kcat is 28 min(-1) with
CC malonyl-AcpM as substrate. kcat is 5 min(-1) with hexadecanoyl-CoA as
CC substrate (PubMed:22017312). {ECO:0000269|PubMed:11600501,
CC ECO:0000269|PubMed:22017312};
CC -!- PATHWAY: Lipid metabolism; mycolic acid biosynthesis.
CC {ECO:0000269|PubMed:12023885, ECO:0000269|PubMed:12464486,
CC ECO:0000305|PubMed:11600501, ECO:0000305|PubMed:19604470}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:19604480}.
CC -!- INTERACTION:
CC P9WQD9; P9WQD9: kasA; NbExp=2; IntAct=EBI-15793653, EBI-15793653;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}.
CC -!- DOMAIN: Phe-404 residue probably plays a key role in the activation of
CC the enzyme at the beginning of the catalytic cycle. A conformational
CC change of Phe-404, possibly triggered by the substrate, is central for
CC the activation because it switches KasA to the sufficiently reactive
CC zwitterionic state. {ECO:0000269|PubMed:24479625}.
CC -!- PTM: Phosphorylated in vitro by several Ser/Thr protein kinases
CC (STPKs). Highly phosphorylated in vivo on threonines. Can be
CC dephosphorylated by the Ser/Thr phosphatase PstP.
CC {ECO:0000269|PubMed:16873379}.
CC -!- MISCELLANEOUS: Identified as a drug target (PubMed:10747933,
CC PubMed:12023885, PubMed:22076471, PubMed:27581223, PubMed:32196311,
CC PubMed:32197094). Inhibited by isoniazid (INH), thiolactomycin (TLM)
CC and related analogs (PubMed:10747933, PubMed:12464486, PubMed:19604480,
CC PubMed:24108128). Highly sensitive to cerulenin (PubMed:12023885). Is
CC the biological target of GSK3011724A, an indazole sulfonamide
CC (PubMed:27581223). Inhibited by the indazole JSF-3285, which is a
CC promising preclinical candidate for tuberculosis (PubMed:32197094).
CC {ECO:0000269|PubMed:10747933, ECO:0000269|PubMed:12023885,
CC ECO:0000269|PubMed:12464486, ECO:0000269|PubMed:19604480,
CC ECO:0000269|PubMed:22076471, ECO:0000269|PubMed:24108128,
CC ECO:0000269|PubMed:27581223, ECO:0000269|PubMed:32196311,
CC ECO:0000269|PubMed:32197094}.
CC -!- SIMILARITY: Belongs to the thiolase-like superfamily. Beta-ketoacyl-ACP
CC synthases family. {ECO:0000305}.
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DR EMBL; AL123456; CCP45025.1; -; Genomic_DNA.
DR PIR; A70779; A70779.
DR RefSeq; NP_216761.1; NC_000962.3.
DR RefSeq; WP_003411571.1; NZ_NVQJ01000008.1.
DR PDB; 2WGD; X-ray; 2.01 A; A=1-416.
DR PDB; 2WGE; X-ray; 1.80 A; A=1-416.
DR PDB; 2WGF; X-ray; 2.15 A; A/B/C/D/E/F/G/H=1-416.
DR PDB; 2WGG; X-ray; 2.00 A; A/B/C/D/E/F/G/H=1-416.
DR PDB; 5LD8; X-ray; 2.13 A; A/B=2-416.
DR PDB; 6P9K; X-ray; 1.70 A; A=3-416.
DR PDB; 6P9L; X-ray; 2.31 A; A=3-416.
DR PDB; 6P9M; X-ray; 2.26 A; A=3-416.
DR PDB; 6Y2I; X-ray; 1.53 A; AAA/BBB=2-416.
DR PDB; 6Y2J; X-ray; 2.89 A; AAA/BBB/CCC/DDD/EEE/FFF/GGG/HHH=2-416.
DR PDBsum; 2WGD; -.
DR PDBsum; 2WGE; -.
DR PDBsum; 2WGF; -.
DR PDBsum; 2WGG; -.
DR PDBsum; 5LD8; -.
DR PDBsum; 6P9K; -.
DR PDBsum; 6P9L; -.
DR PDBsum; 6P9M; -.
DR PDBsum; 6Y2I; -.
DR PDBsum; 6Y2J; -.
DR AlphaFoldDB; P9WQD9; -.
DR SMR; P9WQD9; -.
DR STRING; 83332.Rv2245; -.
DR BindingDB; P9WQD9; -.
DR ChEMBL; CHEMBL4544; -.
DR DrugBank; DB04302; 4-Hydroxy-3,5-Dimethyl-5-(2-Methyl-Buta-1,3-Dienyl)-5h-Thiophen-2-One.
DR SwissLipids; SLP:000000962; -.
DR PaxDb; P9WQD9; -.
DR DNASU; 887269; -.
DR GeneID; 45426225; -.
DR GeneID; 887269; -.
DR KEGG; mtu:Rv2245; -.
DR TubercuList; Rv2245; -.
DR eggNOG; COG0304; Bacteria.
DR OMA; YAYLSMQ; -.
DR PhylomeDB; P9WQD9; -.
DR BioCyc; MetaCyc:G185E-6461-MON; -.
DR BRENDA; 2.3.1.293; 3445.
DR BRENDA; 2.3.1.41; 3445.
DR UniPathway; UPA00915; -.
DR PRO; PR:P9WQD9; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; IDA:MTBBASE.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IDA:MTBBASE.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IBA:GO_Central.
DR GO; GO:0030497; P:fatty acid elongation; IDA:MTBBASE.
DR GO; GO:0019367; P:fatty acid elongation, saturated fatty acid; IDA:MTBBASE.
DR CDD; cd00834; KAS_I_II; 1.
DR Gene3D; 3.40.47.10; -; 2.
DR InterPro; IPR000794; Beta-ketoacyl_synthase.
DR InterPro; IPR014031; Ketoacyl_synth_C.
DR InterPro; IPR014030; Ketoacyl_synth_N.
DR InterPro; IPR020841; PKS_Beta-ketoAc_synthase_dom.
DR InterPro; IPR016039; Thiolase-like.
DR PANTHER; PTHR11712; PTHR11712; 1.
DR Pfam; PF00109; ketoacyl-synt; 1.
DR Pfam; PF02801; Ketoacyl-synt_C; 1.
DR SMART; SM00825; PKS_KS; 1.
DR SUPFAM; SSF53901; SSF53901; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Acyltransferase; Cytoplasm; Fatty acid biosynthesis;
KW Fatty acid metabolism; Lipid biosynthesis; Lipid metabolism;
KW Phosphoprotein; Reference proteome; Transferase.
FT CHAIN 1..416
FT /note="3-oxoacyl-[acyl-carrier-protein] synthase 1"
FT /id="PRO_0000180333"
FT ACT_SITE 171
FT /evidence="ECO:0000305|PubMed:19604480,
FT ECO:0000305|PubMed:24108128, ECO:0000305|PubMed:24479625"
FT BINDING 311
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:19604480,
FT ECO:0000305|PubMed:24108128"
FT BINDING 345
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:19604480,
FT ECO:0000305|PubMed:24108128"
FT SITE 171
FT /note="Interacts with the inhibitor thiolactomycin"
FT /evidence="ECO:0000269|PubMed:19604480,
FT ECO:0000269|PubMed:24108128"
FT SITE 311
FT /note="Interacts with the inhibitor thiolactomycin"
FT /evidence="ECO:0000269|PubMed:19604480,
FT ECO:0000269|PubMed:24108128"
FT SITE 345
FT /note="Interacts with the inhibitor thiolactomycin"
FT /evidence="ECO:0000269|PubMed:19604480,
FT ECO:0000269|PubMed:24108128"
FT MUTAGEN 66
FT /note="D->N: Increases resistance to isoniazid."
FT /evidence="ECO:0000269|PubMed:12464486"
FT MUTAGEN 171
FT /note="C->A: Loss of activity with hexadecanoyl-CoA."
FT /evidence="ECO:0000269|PubMed:12023885"
FT MUTAGEN 171
FT /note="C->Q: Mimics structural changes caused by acyl-
FT enzyme formation."
FT /evidence="ECO:0000269|PubMed:19604480"
FT MUTAGEN 269
FT /note="G->S: Increases resistance to isoniazid."
FT /evidence="ECO:0000269|PubMed:12464486"
FT MUTAGEN 311
FT /note="H->A: Loss of activity with hexadecanoyl-CoA."
FT /evidence="ECO:0000269|PubMed:12023885"
FT MUTAGEN 312
FT /note="G->S: Increases resistance to isoniazid."
FT /evidence="ECO:0000269|PubMed:12464486"
FT MUTAGEN 340
FT /note="K->A: Loss of activity with hexadecanoyl-CoA."
FT /evidence="ECO:0000269|PubMed:12023885"
FT MUTAGEN 345
FT /note="H->A: Loss of activity with hexadecanoyl-CoA."
FT /evidence="ECO:0000269|PubMed:12023885"
FT MUTAGEN 413
FT /note="F->L: Increases resistance to isoniazid."
FT /evidence="ECO:0000269|PubMed:12464486"
FT TURN 6..9
FT /evidence="ECO:0007829|PDB:6P9K"
FT STRAND 14..25
FT /evidence="ECO:0007829|PDB:6P9K"
FT HELIX 29..37
FT /evidence="ECO:0007829|PDB:6P9K"
FT HELIX 49..54
FT /evidence="ECO:0007829|PDB:6P9K"
FT STRAND 60..62
FT /evidence="ECO:0007829|PDB:6P9K"
FT HELIX 68..71
FT /evidence="ECO:0007829|PDB:6P9K"
FT HELIX 74..79
FT /evidence="ECO:0007829|PDB:6P9K"
FT HELIX 82..97
FT /evidence="ECO:0007829|PDB:6P9K"
FT HELIX 105..107
FT /evidence="ECO:0007829|PDB:6P9K"
FT STRAND 108..116
FT /evidence="ECO:0007829|PDB:6P9K"
FT HELIX 120..132
FT /evidence="ECO:0007829|PDB:6P9K"
FT HELIX 134..136
FT /evidence="ECO:0007829|PDB:6P9K"
FT HELIX 141..145
FT /evidence="ECO:0007829|PDB:6P9K"
FT HELIX 149..158
FT /evidence="ECO:0007829|PDB:6P9K"
FT HELIX 170..172
FT /evidence="ECO:0007829|PDB:6P9K"
FT HELIX 173..186
FT /evidence="ECO:0007829|PDB:6P9K"
FT STRAND 191..198
FT /evidence="ECO:0007829|PDB:6P9K"
FT HELIX 204..211
FT /evidence="ECO:0007829|PDB:6P9K"
FT TURN 212..214
FT /evidence="ECO:0007829|PDB:6P9K"
FT HELIX 223..225
FT /evidence="ECO:0007829|PDB:6P9K"
FT STRAND 242..250
FT /evidence="ECO:0007829|PDB:6P9K"
FT HELIX 251..256
FT /evidence="ECO:0007829|PDB:6P9K"
FT STRAND 262..272
FT /evidence="ECO:0007829|PDB:6P9K"
FT STRAND 277..279
FT /evidence="ECO:0007829|PDB:6P9K"
FT HELIX 285..298
FT /evidence="ECO:0007829|PDB:6P9K"
FT HELIX 302..304
FT /evidence="ECO:0007829|PDB:6P9K"
FT STRAND 307..309
FT /evidence="ECO:0007829|PDB:6P9K"
FT HELIX 316..328
FT /evidence="ECO:0007829|PDB:6P9K"
FT STRAND 334..337
FT /evidence="ECO:0007829|PDB:6P9K"
FT HELIX 340..343
FT /evidence="ECO:0007829|PDB:6P9K"
FT HELIX 347..349
FT /evidence="ECO:0007829|PDB:6P9K"
FT HELIX 350..364
FT /evidence="ECO:0007829|PDB:6P9K"
FT TURN 378..380
FT /evidence="ECO:0007829|PDB:2WGE"
FT STRAND 396..403
FT /evidence="ECO:0007829|PDB:6P9K"
FT TURN 404..406
FT /evidence="ECO:0007829|PDB:6P9K"
FT STRAND 407..414
FT /evidence="ECO:0007829|PDB:6P9K"
SQ SEQUENCE 416 AA; 43316 MW; D2187BE2F0B56C7F CRC64;
MSQPSTANGG FPSVVVTAVT ATTSISPDIE STWKGLLAGE SGIHALEDEF VTKWDLAVKI
GGHLKDPVDS HMGRLDMRRM SYVQRMGKLL GGQLWESAGS PEVDPDRFAV VVGTGLGGAE
RIVESYDLMN AGGPRKVSPL AVQMIMPNGA AAVIGLQLGA RAGVMTPVSA CSSGSEAIAH
AWRQIVMGDA DVAVCGGVEG PIEALPIAAF SMMRAMSTRN DEPERASRPF DKDRDGFVFG
EAGALMLIET EEHAKARGAK PLARLLGAGI TSDAFHMVAP AADGVRAGRA MTRSLELAGL
SPADIDHVNA HGTATPIGDA AEANAIRVAG CDQAAVYAPK SALGHSIGAV GALESVLTVL
TLRDGVIPPT LNYETPDPEI DLDVVAGEPR YGDYRYAVNN SFGFGGHNVA LAFGRY
