| Structural highlights
1d6h is a 1 chain structure with sequence from Alfalfa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , |
| NonStd Res: | |
| Related: | 1bi5, 1bq6, 1cgk, 1cgz, 1chw, 1cml |
| Activity: | Naringenin-chalcone synthase, with EC number 2.3.1.74 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
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) catalyzes formation of the phenylpropanoid chalcone from one p-coumaroyl-CoA and three malonyl-coenzyme A (CoA) thioesters. The three-dimensional structure of CHS [Ferrer, J.-L., Jez, J. M., Bowman, M. E., Dixon, R. A., and Noel, J. P. (1999) Nat. Struct. Biol. 6, 775-784] suggests that four residues (Cys164, Phe215, His303, and Asn336) participate in the multiple decarboxylation and condensation reactions catalyzed by this enzyme. Here, we functionally characterize 16 point mutants of these residues for chalcone production, malonyl-CoA decarboxylation, and the ability to bind CoA and acetyl-CoA. Our results confirm Cys164's role as the active-site nucleophile in polyketide formation and elucidate the importance of His303 and Asn336 in the malonyl-CoA decarboxylation reaction. We suggest that Phe215 may help orient substrates at the active site during elongation of the polyketide intermediate. To better understand the structure-function relationships in some of these mutants, we also determined the crystal structures of the CHS C164A, H303Q, and N336A mutants refined to 1.69, 2.0, and 2.15 A resolution, respectively. The structure of the C164A mutant reveals that the proposed oxyanion hole formed by His303 and Asn336 remains undisturbed, allowing this mutant to catalyze malonyl-CoA decarboxylation without chalcone formation. The structures of the H303Q and N336A mutants support the importance of His303 and Asn336 in polarizing the thioester carbonyl of malonyl-CoA during the decarboxylation reaction. In addition, both of these residues may also participate in stabilizing the tetrahedral transition state during polyketide elongation. Conservation of the catalytic functions of the active-site residues may occur across a wide variety of condensing enzymes, including other polyketide and fatty acid synthases.
Dissection of malonyl-coenzyme A decarboxylation from polyketide formation in the reaction mechanism of a plant polyketide synthase.,Jez JM, Ferrer JL, Bowman ME, Dixon RA, Noel JP Biochemistry. 2000 Feb 8;39(5):890-902. PMID:10653632[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, 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
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