Structural highlights
Function
[CHS2_MEDSA] The primary product of this enzyme is 4,2',4',6'-tetrahydroxychalcone (also termed naringenin-chalcone or chalcone) which can under specific conditions spontaneously isomerize into naringenin.[1] [2] [3] [4]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Chalcone synthase (CHS) belongs to the family of type III polyketide synthases (PKS) that catalyze formation of structurally diverse polyketides. CHS synthesizes a tetraketide by sequential condensation of three acetyl anions derived from malonyl-CoA decarboxylation to a p-coumaroyl moiety attached to an active site cysteine. Gly256 resides on the surface of the CHS active site that is in direct contact with the polyketide chain derived from malonyl-CoA. Thus, position 256 serves as an ideal target to probe the link between cavity volume and polyketide chain-length determination in type III PKS. Functional examination of CHS G256A, G256V, G256L, and G256F mutants reveals altered product profiles from that of wild-type CHS. With p-coumaroyl-CoA as a starter molecule, the G256A and G256V mutants produce notably more tetraketide lactone. Further restrictions in cavity volume such as that seen in the G256L and G256F mutants yield increasing levels of the styrylpyrone bis-noryangonin from a triketide intermediate. X-ray crystallographic structures of the CHS G256A, G256V, G256L, and G256F mutants establish that these substitutions reduce the size of the active site cavity without significant alterations in the conformations of the polypeptide backbones. The side chain volume of position 256 influences both the number of condensation reactions during polyketide chain extension and the conformation of the triketide and tetraketide intermediates during the cyclization reaction. These results viewed in conjunction with the natural sequence variation of residue 256 suggest that rapid diversification of product specificity without concomitant loss of substantial catalytic activity in related CHS-like enzymes can occur by site-specific evolution of side chain volume at position 256.
Structure-guided programming of polyketide chain-length determination in chalcone synthase.,Jez JM, Bowman ME, Noel JP Biochemistry. 2001 Dec 11;40(49):14829-38. PMID:11732902[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Jez JM, Ferrer JL, Bowman ME, Dixon RA, Noel JP. Dissection of malonyl-coenzyme A decarboxylation from polyketide formation in the reaction mechanism of a plant polyketide synthase. Biochemistry. 2000 Feb 8;39(5):890-902. PMID:10653632
- ↑ Jez JM, Bowman ME, Noel JP. Structure-guided programming of polyketide chain-length determination in chalcone synthase. Biochemistry. 2001 Dec 11;40(49):14829-38. PMID:11732902
- ↑ Jez JM, Bowman ME, Noel JP. Expanding the biosynthetic repertoire of plant type III polyketide synthases by altering starter molecule specificity. Proc Natl Acad Sci U S A. 2002 Apr 16;99(8):5319-24. PMID:11959984 doi:10.1073/pnas.082590499
- ↑ Austin MB, Bowman ME, Ferrer JL, Schroder J, Noel JP. An aldol switch discovered in stilbene synthases mediates cyclization specificity of type III polyketide synthases. Chem Biol. 2004 Sep;11(9):1179-94. PMID:15380179 doi:http://dx.doi.org/10.1016/j.chembiol.2004.05.024
- ↑ Jez JM, Bowman ME, Noel JP. Structure-guided programming of polyketide chain-length determination in chalcone synthase. Biochemistry. 2001 Dec 11;40(49):14829-38. PMID:11732902
