1u0u

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1u0u, resolution 2.11Å

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An Aldol Switch Discovered in Stilbene Synthases Mediates Cyclization Specificity of Type III Polyketide Synthases: Pine stilbene synthase structure

Overview

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.

About this Structure

1U0U is a Single protein structure of sequence from Pinus sylvestris. Full crystallographic information is available from OCA.

Reference

An aldol switch discovered in stilbene synthases mediates cyclization specificity of type III polyketide synthases., Austin MB, Bowman ME, Ferrer JL, Schroder J, Noel JP, Chem Biol. 2004 Sep;11(9):1179-94. PMID:15380179

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