PKS11_MYCTU
ID PKS11_MYCTU Reviewed; 353 AA.
AC P9WPF3; L0T8X6; O06587; Q7D871;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 40.
DE RecName: Full=Methyl-branched alkylpyrone synthesis polyketide synthase-like Pks11 {ECO:0000305};
DE EC=2.3.1.- {ECO:0000269|PubMed:12941968, ECO:0000269|PubMed:23615910};
DE AltName: Full=Chalcone synthase-like protein;
DE Short=CHS-like;
DE AltName: Full=Methyl-branched alkylpyrone synthesis polyketide synthase type III Pks11 {ECO:0000305};
GN Name=pks11; OrderedLocusNames=Rv1665;
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 AS A POLYKETIDE SYNTHASE, STARTER UNIT SPECIFICITY, AND CATALYTIC
RP ACTIVITY.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=12941968; DOI=10.1074/jbc.m306714200;
RA Saxena P., Yadav G., Mohanty D., Gokhale R.S.;
RT "A new family of type III polyketide synthases in Mycobacterium
RT tuberculosis.";
RL J. Biol. Chem. 278:44780-44790(2003).
RN [3]
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 [4] {ECO:0007744|PDB:4JAO, ECO:0007744|PDB:4JAP, ECO:0007744|PDB:4JAQ, ECO:0007744|PDB:4JAR, ECO:0007744|PDB:4JAT, ECO:0007744|PDB:4JD3}
RP X-RAY CRYSTALLOGRAPHY (1.73 ANGSTROMS) IN COMPLEXES WITH PALMITATE;
RP COENZYME A AND POLYKETIDE INTERMEDIATES, FUNCTION, CATALYTIC ACTIVITY,
RP SUBUNIT, ACTIVE SITE, AND MUTAGENESIS OF CYS-138.
RX PubMed=23615910; DOI=10.1074/jbc.m113.468892;
RA Gokulan K., O'Leary S.E., Russell W.K., Russell D.H., Lalgondar M.,
RA Begley T.P., Ioerger T.R., Sacchettini J.C.;
RT "Crystal structure of Mycobacterium tuberculosis polyketide synthase 11
RT (PKS11) reveals intermediates in the synthesis of methyl-branched
RT alkylpyrones.";
RL J. Biol. Chem. 288:16484-16494(2013).
CC -!- FUNCTION: Involved in the biosynthesis of methyl-branched alkylpyrones
CC (PubMed:23615910). Pks11 catalyzes the extension of medium- and long-
CC chain aliphatic acyl-CoA substrates by using malonyl-CoA and
CC methylmalonyl-CoA as extender molecules to synthesize polyketide
CC products (PubMed:12941968, PubMed:23615910). Palmitoyl-CoA or a similar
CC long chain fatty acid derivative is the likely substrate in vivo
CC (PubMed:23615910). {ECO:0000269|PubMed:12941968,
CC ECO:0000269|PubMed:23615910}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 H(+) + hexadecanoyl-CoA + malonyl-CoA + methylmalonyl-CoA =
CC 4-hydroxy-5-methyl-6-pentadecylpyran-2-one + 2 CO2 + 3 CoA;
CC Xref=Rhea:RHEA:44296, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57379, ChEBI:CHEBI:57384,
CC ChEBI:CHEBI:59916, ChEBI:CHEBI:84253;
CC Evidence={ECO:0000269|PubMed:23615910};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44297;
CC Evidence={ECO:0000269|PubMed:23615910};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 H(+) + malonyl-CoA + methylmalonyl-CoA + octadecanoyl-CoA =
CC 4-hydroxy-5-methyl-6-heptadecylpyran-2-one + 2 CO2 + 3 CoA;
CC Xref=Rhea:RHEA:44300, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57384, ChEBI:CHEBI:57394,
CC ChEBI:CHEBI:59916, ChEBI:CHEBI:84255;
CC Evidence={ECO:0000269|PubMed:23615910};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44301;
CC Evidence={ECO:0000269|PubMed:23615910};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 H(+) + hexanoyl-CoA + 2 malonyl-CoA = 4-hydroxy-6-
CC pentylpyran-2-one + 2 CO2 + 3 CoA; Xref=Rhea:RHEA:43452,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57384, ChEBI:CHEBI:62620, ChEBI:CHEBI:66958;
CC Evidence={ECO:0000269|PubMed:12941968};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43453;
CC Evidence={ECO:0000269|PubMed:12941968};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dodecanoyl-CoA + 2 H(+) + 2 malonyl-CoA = 4-hydroxy-6-
CC undecylpyran-2-one + 2 CO2 + 3 CoA; Xref=Rhea:RHEA:43460,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57375, ChEBI:CHEBI:57384, ChEBI:CHEBI:84149;
CC Evidence={ECO:0000269|PubMed:12941968};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43461;
CC Evidence={ECO:0000269|PubMed:12941968};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dodecanoyl-CoA + 3 H(+) + 3 malonyl-CoA = 4-hydroxy-6-(2-
CC oxotridecyl)pyran-2-one + 3 CO2 + 4 CoA; Xref=Rhea:RHEA:43368,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57375, ChEBI:CHEBI:57384, ChEBI:CHEBI:84150;
CC Evidence={ECO:0000269|PubMed:12941968};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43369;
CC Evidence={ECO:0000269|PubMed:12941968};
CC -!- PATHWAY: Lipid metabolism; fatty acid biosynthesis.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:23615910}.
CC -!- SIMILARITY: Belongs to the thiolase-like superfamily. Chalcone/stilbene
CC synthases family. {ECO:0000305}.
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DR EMBL; AL123456; CCP44430.1; -; Genomic_DNA.
DR PIR; C70985; C70985.
DR RefSeq; NP_216181.1; NC_000962.3.
DR RefSeq; WP_003408248.1; NZ_NVQJ01000010.1.
DR PDB; 4JAO; X-ray; 2.05 A; A/B/C/D=1-353.
DR PDB; 4JAP; X-ray; 1.83 A; A/B/C/D=1-353.
DR PDB; 4JAQ; X-ray; 1.73 A; A/B/C/D=1-353.
DR PDB; 4JAR; X-ray; 1.98 A; A/B/C/D=1-353.
DR PDB; 4JAT; X-ray; 2.42 A; A/B/C/D=1-353.
DR PDB; 4JD3; X-ray; 2.25 A; A/B/C/D=1-353.
DR PDBsum; 4JAO; -.
DR PDBsum; 4JAP; -.
DR PDBsum; 4JAQ; -.
DR PDBsum; 4JAR; -.
DR PDBsum; 4JAT; -.
DR PDBsum; 4JD3; -.
DR AlphaFoldDB; P9WPF3; -.
DR SMR; P9WPF3; -.
DR STRING; 83332.Rv1665; -.
DR SwissLipids; SLP:000001036; -.
DR PaxDb; P9WPF3; -.
DR DNASU; 885525; -.
DR GeneID; 45425634; -.
DR GeneID; 885525; -.
DR KEGG; mtu:Rv1665; -.
DR TubercuList; Rv1665; -.
DR eggNOG; COG3424; Bacteria.
DR OMA; NFMGCYA; -.
DR PhylomeDB; P9WPF3; -.
DR UniPathway; UPA00094; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0034081; C:polyketide synthase complex; IMP:UniProtKB.
DR GO; GO:0016747; F:acyltransferase activity, transferring groups other than amino-acyl groups; IBA:GO_Central.
DR GO; GO:0009715; P:chalcone biosynthetic process; IDA:MTBBASE.
DR GO; GO:0071770; P:DIM/DIP cell wall layer assembly; IMP:MTBBASE.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0008610; P:lipid biosynthetic process; IMP:MTBBASE.
DR GO; GO:0030639; P:polyketide biosynthetic process; IBA:GO_Central.
DR Gene3D; 3.40.47.10; -; 2.
DR InterPro; IPR012328; Chalcone/stilbene_synt_C.
DR InterPro; IPR001099; Chalcone/stilbene_synt_N.
DR InterPro; IPR011141; Polyketide_synthase_type-III.
DR InterPro; IPR016039; Thiolase-like.
DR PANTHER; PTHR11877; PTHR11877; 1.
DR Pfam; PF02797; Chal_sti_synt_C; 1.
DR Pfam; PF00195; Chal_sti_synt_N; 1.
DR PIRSF; PIRSF000451; PKS_III; 1.
DR SUPFAM; SSF53901; SSF53901; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acyltransferase; Fatty acid metabolism; Lipid metabolism;
KW Reference proteome; Transferase.
FT CHAIN 1..353
FT /note="Methyl-branched alkylpyrone synthesis polyketide
FT synthase-like Pks11"
FT /id="PRO_0000407318"
FT ACT_SITE 138
FT /note="Nucleophile"
FT /evidence="ECO:0000305|PubMed:23615910"
FT BINDING 180
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:23615910"
FT BINDING 241
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:23615910"
FT BINDING 277..282
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:23615910"
FT BINDING 312
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:23615910"
FT MUTAGEN 138
FT /note="C->S: Can catalyze the hydrolysis of palmitoyl-CoA,
FT but cannot produce cyclic polyketide products."
FT /evidence="ECO:0000269|PubMed:23615910"
FT STRAND 3..10
FT /evidence="ECO:0007829|PDB:4JAQ"
FT STRAND 15..17
FT /evidence="ECO:0007829|PDB:4JAQ"
FT HELIX 18..25
FT /evidence="ECO:0007829|PDB:4JAQ"
FT TURN 29..31
FT /evidence="ECO:0007829|PDB:4JAQ"
FT HELIX 32..34
FT /evidence="ECO:0007829|PDB:4JAQ"
FT HELIX 35..43
FT /evidence="ECO:0007829|PDB:4JAQ"
FT STRAND 49..51
FT /evidence="ECO:0007829|PDB:4JAQ"
FT HELIX 56..61
FT /evidence="ECO:0007829|PDB:4JAQ"
FT HELIX 65..91
FT /evidence="ECO:0007829|PDB:4JAQ"
FT HELIX 95..97
FT /evidence="ECO:0007829|PDB:4JAQ"
FT STRAND 99..107
FT /evidence="ECO:0007829|PDB:4JAQ"
FT HELIX 114..122
FT /evidence="ECO:0007829|PDB:4JAQ"
FT STRAND 129..135
FT /evidence="ECO:0007829|PDB:4JAQ"
FT HELIX 137..139
FT /evidence="ECO:0007829|PDB:4JAQ"
FT HELIX 140..154
FT /evidence="ECO:0007829|PDB:4JAQ"
FT STRAND 159..167
FT /evidence="ECO:0007829|PDB:4JAQ"
FT HELIX 168..174
FT /evidence="ECO:0007829|PDB:4JAQ"
FT HELIX 179..187
FT /evidence="ECO:0007829|PDB:4JAQ"
FT STRAND 190..198
FT /evidence="ECO:0007829|PDB:4JAQ"
FT HELIX 200..203
FT /evidence="ECO:0007829|PDB:4JAQ"
FT TURN 204..207
FT /evidence="ECO:0007829|PDB:4JAP"
FT STRAND 212..220
FT /evidence="ECO:0007829|PDB:4JAQ"
FT STRAND 227..233
FT /evidence="ECO:0007829|PDB:4JAQ"
FT STRAND 236..241
FT /evidence="ECO:0007829|PDB:4JAQ"
FT HELIX 245..262
FT /evidence="ECO:0007829|PDB:4JAQ"
FT TURN 263..265
FT /evidence="ECO:0007829|PDB:4JAQ"
FT HELIX 268..270
FT /evidence="ECO:0007829|PDB:4JAQ"
FT STRAND 271..276
FT /evidence="ECO:0007829|PDB:4JAQ"
FT HELIX 281..290
FT /evidence="ECO:0007829|PDB:4JAQ"
FT TURN 295..298
FT /evidence="ECO:0007829|PDB:4JAQ"
FT HELIX 299..308
FT /evidence="ECO:0007829|PDB:4JAQ"
FT HELIX 312..314
FT /evidence="ECO:0007829|PDB:4JAQ"
FT HELIX 315..325
FT /evidence="ECO:0007829|PDB:4JAQ"
FT STRAND 333..340
FT /evidence="ECO:0007829|PDB:4JAQ"
FT TURN 341..343
FT /evidence="ECO:0007829|PDB:4JAQ"
FT STRAND 344..351
FT /evidence="ECO:0007829|PDB:4JAQ"
SQ SEQUENCE 353 AA; 37639 MW; 1F2225FC7D41AA17 CRC64;
MSVIAGVFGA LPPHRYSQSE ITDSFVEFPG LKEHEEIIRR LHAAAKVNGR HLVLPLQQYP
SLTDFGDANE IFIEKAVDLG VEALLGALDD ANLRPSDIDM IATATVTGVA VPSLDARIAG
RLGLRPDVRR MPLFGLGCVA GAAGVARLRD YLRGAPDDVA VLVSVELCSL TYPAVKPTVS
SLVGTALFGD GAAAVVAVGD RRAEQVRAGG PDILDSRSSL YPDSLHIMGW DVGSHGLRLR
LSPDLTNLIE RYLANDVTTF LDAHRLTKDD IGAWVSHPGG PKVIDAVATS LALPPEALEL
TWRSLGEIGN LSSASILHIL RDTIEKRPPS GSAGLMLAMG PGFCTELVLL RWR
