1U0U: An Aldol Switch Discovered In Stilbene Synthases Mediates Cyclization Specificity Of Type Iii Polyketide Synthases: Pine Stilbene Synthase Structure

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.
PDB ID: 1U0UDownload
MMDB ID: 29985
PDB Deposition Date: 2004/7/14
Updated in MMDB: 2004/12
Experimental Method:
x-ray diffraction
Resolution: 2.11  Å
Source Organism:
Similar Structures:
Biological Unit for 1U0U: dimeric; determined by author and by software (PISA)
Molecular Components in 1U0U
Label Count Molecule
Proteins (2 molecules)
Dihydropinosylvin Synthase
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB