1U0V

An Aldol Switch Discovered in Stilbene Synthases Mediates Cyclization of Specificity of Type III Polyketide Synthases: 18xCHS structure

Summary for 1U0V

• Entry DOI: 10.2210/pdb1u0v/pdb
• Related: 1BI5 1U0U 1U0W
• Descriptor: Chalcone synthase 2 (2 entities in total)
• Functional Keywords: type iii polyketide synthase, pks, condensing enzyme, thiolase fold, alpha-beta-alpha-beta-alpha fold, aldol switch, catalytic triad, engineered resveratrol synthase, transferase
• Biological source: Medicago sativa
• Total number of polymer chains: 2
• Total formula weight: 85748.65

Authors

Austin, M.B.,Bowman, M.E.,Ferrer, J.-L.,Schroder, J.,Noel, J.P. (deposition date: 2004-07-14, release date: 2004-10-12, Last modification date: 2023-08-23)

Primary citation

Austin, M.B.,Bowman, M.E.,Ferrer, J.-L.,Schroder, J.,Noel, J.P.
An Aldol Switch Discovered in Stilbene Synthases Mediates Cyclization Specificity of Type III Polyketide Synthases
Chem.Biol., 11:1179-1194, 2004

PubMed Abstract: Stilbene synthase (STS) and chalcone synthase (CHS) each catalyze the formation of a tetraketide intermediate from a CoA-tethered phenylpropanoid starter and three molecules of malonyl-CoA, but use different cyclization mechanisms to produce distinct chemical scaffolds for a variety of plant natural products. Here we present the first STS crystal structure and identify, by mutagenic conversion of alfalfa CHS into a functional stilbene synthase, the structural basis for the evolution of STS cyclization specificity in type III polyketide synthase (PKS) enzymes. Additional mutagenesis and enzymatic characterization confirms that electronic effects rather than steric factors balance competing cyclization specificities in CHS and STS. Finally, we discuss the problematic in vitro reconstitution of plant stilbenecarboxylate pathways, using insights from existing biomimetic polyketide cyclization studies to generate a novel mechanistic hypothesis to explain stilbenecarboxylate biosynthesis.

PubMed: 15380179
DOI: 10.1016/j.chembiol.2004.05.024

Experimental method

X-RAY DIFFRACTION (1.9 Å)