EzCatDB: D00411

DB codeD00411
CATH domainDomain 13.40.47.10Catalytic domain
Domain 23.40.47.10Catalytic domain
E.C.2.3.1.74
CSA1cgk

CATH domainRelated DB codes (homologues)
3.40.47.10D00090,D00509,D00825,D00826,D00867,D00871

Enzyme Name
Swiss-protKEGG

P30074
Protein nameChalcone synthase 2naringenin-chalcone synthase
chalcone synthase
flavanone synthase
6'-deoxychalcone synthase
chalcone synthetase
DOCS
CHS
SynonymsEC 2.3.1.74
Naringenin-chalcone synthase 2

KEGG pathways
MAP codePathways
MAP00941Flavonoid biosynthesis

Swiss-prot:Accession NumberP30074
Entry nameCHS2_MEDSA
Activity3 malonyl-CoA + 4-coumaroyl-CoA = 4 CoA + naringenin chalcone + 3 CO(2).
Subunit
Subcellular location
Cofactor


SubstratesProductsintermediates
KEGG-idC00083C00223C00010C06561C00011








CompoundMalonyl-CoA4-Coumaroyl-CoACoANaringenin chalconeCO2Monoketide intermediateEnolic acetyl-CoADiketide CoA thioesterDiketide intermediateTriketide CoA thioesterTriketide intermediateTetraketide CoA thioesterTetraketide intermediateCyclized tetraketide
Typeamine group,carbohydrate,carboxyl group,nucleotide,peptide/protein,sulfide groupamine group,aromatic ring (only carbon atom),carbohydrate,nucleotide,peptide/protein,sulfide groupamine group,carbohydrate,nucleotide,peptide/protein,sulfhydryl grouparomatic ring (only carbon atom),carbohydrateothers








1bi5A01UnboundUnboundUnboundUnboundUnboundUnbound







1bq6A01UnboundUnboundBound:COAUnboundUnboundUnbound







1cgkA01UnboundUnboundUnboundAnalogue:NARUnboundUnbound







1cgzA01UnboundUnboundUnboundAnalogue:STLUnboundUnbound







1chwA01UnboundUnboundUnboundUnboundUnboundUnbound







1chwB01UnboundUnboundUnboundUnboundUnboundUnbound







1cmlA01Analogue:MLCUnboundUnboundUnboundUnboundIntermediate-analogue:PIN







1d6fA01UnboundUnboundUnboundUnboundUnboundUnbound







1d6hA01UnboundUnboundBound:COAUnboundUnboundUnbound







1d6iA01UnboundUnboundUnboundUnboundUnboundUnbound







1d6iB01UnboundUnboundUnboundUnboundUnboundUnbound







1i86A01UnboundUnboundUnboundUnboundUnboundUnbound







1i88A01UnboundUnboundUnboundUnboundUnboundUnbound







1i88B01UnboundUnboundUnboundUnboundUnboundUnbound







1i89A01UnboundUnboundUnboundUnboundUnboundUnbound







1i89B01UnboundUnboundUnboundUnboundUnboundUnbound







1i8bA01UnboundUnboundUnboundUnboundUnboundUnbound







1i8bB01UnboundUnboundUnboundUnboundUnboundUnbound







1jwxA01UnboundUnboundUnboundUnboundUnboundUnbound







1u0vA01UnboundUnboundUnboundUnboundUnboundUnbound







1u0vB01UnboundUnboundUnboundUnboundUnboundUnbound







1u0wA01UnboundUnboundUnboundAnalogue:STLUnboundUnbound







1u0wB01UnboundUnboundUnboundAnalogue:STLUnboundUnbound







1u0wC01UnboundUnboundUnboundAnalogue:STLUnboundUnbound







1u0wD01UnboundUnboundUnboundAnalogue:STLUnboundUnbound







1bi5A02UnboundUnboundUnboundUnboundUnboundUnbound







1bq6A02UnboundUnboundUnboundUnboundUnboundUnbound







1cgkA02UnboundUnboundUnboundUnboundUnboundUnbound







1cgzA02UnboundUnboundUnboundUnboundUnboundUnbound







1chwA02UnboundAnalogue:HXCUnboundUnboundUnboundUnbound







1chwB02UnboundAnalogue:HXCUnboundUnboundUnboundUnbound







1cmlA02UnboundUnboundUnboundUnboundUnboundUnbound







1d6fA02UnboundUnboundUnboundUnboundUnboundUnbound







1d6hA02UnboundUnboundUnboundUnboundUnboundUnbound







1d6iA02UnboundUnboundUnboundUnboundUnboundUnbound







1d6iB02UnboundUnboundUnboundUnboundUnboundUnbound







1i86A02UnboundUnboundUnboundUnboundUnboundUnbound







1i88A02UnboundUnboundUnboundUnboundUnboundUnbound







1i88B02UnboundUnboundUnboundUnboundUnboundUnbound







1i89A02UnboundUnboundUnboundUnboundUnboundUnbound







1i89B02UnboundUnboundUnboundUnboundUnboundUnbound







1i8bA02UnboundUnboundUnboundUnboundUnboundUnbound







1i8bB02UnboundUnboundUnboundUnboundUnboundUnbound







1jwxA02UnboundUnboundUnboundUnboundUnboundUnbound







1u0vA02UnboundUnboundUnboundUnboundUnboundUnbound







1u0vB02UnboundUnboundUnboundUnboundUnboundUnbound







1u0wA02UnboundUnboundUnboundUnboundUnboundUnbound







1u0wB02UnboundUnboundUnboundUnboundUnboundUnbound







1u0wC02UnboundUnboundUnboundUnboundUnboundUnbound







1u0wD02UnboundUnboundUnboundUnboundUnboundUnbound








Active-site residues
resource
PDB;1bi5, 1bq6, 1cgk, 1cgz, 1chw & Swiss-prot;P48391
pdbCatalytic residuesModified residuescomment
1bi5A01       ;PHE 215
CSD 164(S-sulfinocysteine)

1bq6A01       ;PHE 215
CSD 164(S-sulfinocysteine)

1cgkA01CYS 164;PHE 215
                          

1cgzA01CYS 164;PHE 215
                          

1chwA01       ;PHE 215
                          
mutant C164S
1chwB01       ;PHE 215
                          
mutant C164S
1cmlA01       ;PHE 215
                          
mutant C164A
1d6fA01       ;PHE 215
                          
mutant C164A
1d6hA01       ;PHE 215
CSD 164(S-sulfinocysteine)

1d6iA01       ;PHE 215
CSD 164(S-sulfinocysteine)

1d6iB01       ;PHE 215
CSD 164(S-sulfinocysteine)

1i86A01       ;PHE 215
CSD 164(S-sulfinocysteine)

1i88A01       ;PHE 215
CSD 164(S-sulfinocysteine)

1i88B01       ;PHE 215
CSD 164(S-sulfinocysteine)

1i89A01       ;PHE 215
CSD 164(S-sulfinocysteine)

1i89B01       ;PHE 215
CSD 164(S-sulfinocysteine)

1i8bA01       ;PHE 215
CSD 164(S-sulfinocysteine)

1i8bB01       ;PHE 215
CSD 164(S-sulfinocysteine)

1jwxA01       ;       
CSD 164(S-sulfinocysteine)
mutant F215S
1u0vA01CYS 164;PHE 215
                          

1u0vB01CYS 164;PHE 215
                          

1u0wA01CYS 164;PHE 215
                          

1u0wB01CYS 164;PHE 215
                          

1u0wC01CYS 164;PHE 215
                          

1u0wD01CYS 164;PHE 215
                          

1bi5A02HIS 303;ASN 336


1bq6A02HIS 303;ASN 336


1cgkA02HIS 303;ASN 336


1cgzA02HIS 303;ASN 336


1chwA02HIS 303;ASN 336


1chwB02HIS 303;ASN 336


1cmlA02HIS 303;ASN 336


1d6fA02HIS 303;ASN 336


1d6hA02HIS 303;       

mutant N336A
1d6iA02       ;ASN 336

mutant H303Q
1d6iB02       ;ASN 336

mutant H303Q
1i86A02HIS 303;ASN 336


1i88A02HIS 303;ASN 336


1i88B02HIS 303;ASN 336


1i89A02HIS 303;ASN 336


1i89B02HIS 303;ASN 336


1i8bA02HIS 303;ASN 336


1i8bB02HIS 303;ASN 336


1jwxA02HIS 303;ASN 336


1u0vA02HIS 303;ASN 336


1u0vB02HIS 303;ASN 336


1u0wA02HIS 303;ASN 336


1u0wB02HIS 303;ASN 336


1u0wC02HIS 303;ASN 336


1u0wD02HIS 303;ASN 336



References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[5]Fig.6, p.778-7828
[6]Fig.1, p.39642-396452
[7]Fig.1, Fig.9, p.898-9002
[9]Fig.4, p.394-3972
[11]Fig.1, p.14836-143874
[14]Fig.1, Fig.6, p.45169-45174
[15]Fig.1, Fig.5, Fig.6

references
[1]
PubMed ID6853502
JournalJ Biol Chem
Year1983
Volume258
Pages6730-4
AuthorsSchuz R, Heller W, Hahlbrock K
TitleSubstrate specificity of chalcone synthase from Petroselinum hortense. Formation of phloroglucinol derivatives from aliphatic substrates.
[2]
PubMed ID3777940
JournalArch Biochem Biophys
Year1986
Volume250
Pages364-72
AuthorsKnogge W, Schmelzer E, Weissenbock G
TitleThe role of chalcone synthase in the regulation of flavonoid biosynthesis in developing oat primary leaves.
[3]
PubMed ID7713888
JournalJ Biol Chem
Year1995
Volume270
Pages7922-8
AuthorsTropf S, Karcher B, Schroder G, Schroder J
TitleReaction mechanisms of homodimeric plant polyketide synthase (stilbenes and chalcone synthase). A single active site for the condensing reaction is sufficient for synthesis of stilbenes, chalcones, and 6'-deoxychalcones.
[4]
PubMed ID10476972
JournalNature
Year1999
Volume400
Pages897-9
AuthorsFuna N, Ohnishi Y, Fujii I, Shibuya M, Ebizuka Y, Horinouchi S
TitleA new pathway for polyketide synthesis in microorganisms.
[5]
CommentsX-ray crystallography
PubMed ID10426957
JournalNat Struct Biol
Year1999
Volume6
Pages775-84
AuthorsFerrer JL, Jez JM, Bowman ME, Dixon RA, Noel JP
TitleStructure of chalcone synthase and the molecular basis of plant polyketide biosynthesis.
Related PDB1bi5,1bq6,1cgk,1cgz,1chw,1cml
[6]
PubMed ID11006298
JournalJ Biol Chem
Year2000
Volume275
Pages39640-6
AuthorsJez JM, Noel JP
TitleMechanism of chalcone synthase. pKa of the catalytic cysteine and the role of the conserved histidine in a plant polyketide synthase.
[7]
CommentsX-RAY CRYSTALLOGRAPHY (1.69 ANGSTROMS)
Medline ID20120577
PubMed ID10653632
JournalBiochemistry
Year2000
Volume39
Pages890-902
AuthorsJez JM, Ferrer JL, Bowman ME, Dixon RA, Noel JP
TitleDissection of malonyl-coenzyme A decarboxylation from polyketide formation in the reaction mechanism of a plant polyketide synthase.
Related PDB1d6f,1d6h,1d6i
Related Swiss-protP30074
[8]
PubMed ID10973790
JournalBiochem Biophys Res Commun
Year2000
Volume275
Pages725-30
AuthorsSuh DY, Kagami J, Fukuma K, Sankawa U
TitleEvidence for catalytic cysteine-histidine dyad in chalcone synthase.
[9]
PubMed ID11774005
JournalJ Ind Microbiol Biotechnol
Year2001
Volume27
Pages393-8
AuthorsJez JM, Ferrer JL, Bowman ME, Austin MB, Schroder J, Dixon RA, Noel JP
TitleStructure and mechanism of chalcone synthase-like polyketide synthases.
[10]
PubMed ID11728463
JournalFEBS Lett
Year2001
Volume508
Pages413-7
AuthorsLukacin R, Schreiner S, Matern U
TitleTransformation of acridone synthase to chalcone synthase.
[11]
PubMed ID11732902
JournalBiochemistry
Year2001
Volume40
Pages14829-38
AuthorsJez JM, Bowman ME, Noel JP
TitleStructure-guided programming of polyketide chain-length determination in chalcone synthase.
Related PDB1i86,1i88,1i89,1i8b
[12]
PubMed ID11959984
JournalProc Natl Acad Sci U S A
Year2002
Volume99
Pages5319-24
AuthorsJez JM, Bowman ME, Noel JP
TitleExpanding the biosynthetic repertoire of plant type III polyketide synthases by altering starter molecule specificity.
Related PDB1jwx
[13]
PubMed ID12502351
JournalJ Nat Prod
Year2002
Volume65
Pages1956-62
AuthorsMoore BS, Hertweck C, Hopke JN, Izumikawa M, Kalaitzis JA, Nilsen G, O'Hare T, Piel J, Shipley PR, Xiang L, Austin MB, Noel JP
TitlePlant-like biosynthetic pathways in bacteria: from benzoic acid to chalcone.
[14]
PubMed ID15265863
JournalJ Biol Chem
Year2004
Volume279
Pages45162-74
AuthorsAustin MB, Izumikawa M, Bowman ME, Udwary DW, Ferrer JL, Moore BS, Noel JP
TitleCrystal structure of a bacterial type III polyketide synthase and enzymatic control of reactive polyketide intermediates.
[15]
PubMed ID15380179
JournalChem Biol
Year2004
Volume11
Pages1179-94
AuthorsAustin MB, Bowman ME, Ferrer JL, Schroder J, Noel JP
TitleAn aldol switch discovered in stilbene synthases mediates cyclization specificity of type III polyketide synthases.
Related PDB1u0v,1u0w

comments
According to the literature [5], this enzyme catalyzes the following reactions:
(A) Transfer of acyl group from sulfur atom of coumaronyl-CoA to the nucleophilic cysteine residue, forming monoketide intermediate:
(B) Eliminative double-bond formation; Elimination of CO2 from malonyl-CoA, giving enolic acetyl-CoA:
(C) Transfer of acyl group (monoketide) from the cysteine residue to the carbon atom of enolic acetyl-CoA, forming diketide CoA thioester:
(D) Transfer of acyl group (diketide) from sulfur atom of diketide CoA thioester to the cysteine residue, forming diketide intermediate:
(E) Eliminative double-bond formation; Elimination of CO2 from malonyl-CoA, giving enolic acetyl-CoA:
(F) Transfer of acyl group (diketide) from the cysteine residue to the carbon atom of enolic acetyl-CoA, forming triketide CoA thioester:
(G) Transfer of acyl group (triketide) from sulfur atom of triketide CoA thioester to the cysteine residue, forming triketide intermediate:
(H) Eliminative double-bond formation; Elimination of CO2 from malonyl-CoA, giving enolic acetyl-CoA:
(I) Transfer of acyl group (triketide) from the cysteine residue to the carbon atom of enolic acetyl-CoA, forming tetraketide CoA thioester:
(J) Transfer of acyl group (tetraketide) from sulfur atom of triketide CoA thioester to the cysteine residue, forming tetraketide intermediate:
(K) Intramolecular transfer of acyl group from the cysteine to the methylene carbon of the tetraketide intermediate (Cyclization):
(L) Isomerization of carbonyl oxygen to hydroxyl oxygen (Aromatization):

createdupdated
2002-11-252009-02-26


Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2010)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)

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