9C3W

Crystal structure of biphenyl synthase from Malus domestica complexed with diketide-CoA mimetics

This is a non-PDB format compatible entry.

Summary for 9C3W

• Entry DOI: 10.2210/pdb9c3w/pdb
• Descriptor: BIS3 biphenyl synthase, (3R)-butane-1,3-diol, [(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-4-hydroxy-3-(phosphonooxy)oxolan-2-yl]methyl (3R)-3-hydroxy-2,2-dimethyl-4-oxo-4-{[3-oxo-3-({2-[2-(2-phenyl-1,3-dioxolan-2-yl)acetamido]ethyl}amino)propyl]amino}butyl dihydrogen diphosphate, ... (5 entities in total)
• Functional Keywords: polyketide synthase, transferase, coa analog
• Biological source: Malus domestica (apple)
• Total number of polymer chains: 2
• Total formula weight: 88580.83

Authors

Re, R.N.,Noel, J.P.,Burkart, M.D. (deposition date: 2024-06-02, release date: 2025-05-14, Last modification date: 2025-05-21)

Primary citation

Re, R.N.,La Clair, J.J.,Noel, J.P.,Burkart, M.D.
Elucidating the Iterative Elongation Mechanism in a Type III Polyketide Synthase.
J.Am.Chem.Soc., 147:16705-16714, 2025

PubMed Abstract: Type III polyketide synthases (PKSs) have a much simpler three-dimensional architecture compared with their type I and type II counterparts, yet they catalyze iterative polyketide elongation to generate a myriad of products in plants, fungi, and eubacteria. Despite this mechanistic complexity occurring within a single active site, the mechanism by which type III PKSs stabilize and direct their highly reactive keto and enolate intermediates has yet to be fully understood. Here, we report the synthesis and deployment of stable polyketone CoA analogues for each putative intermediate involved in the biphenyl synthase (BIS) mechanism together with three high-resolution crystal structures of each in complex with BIS from . This set of structures reveals key mechanistic features that control the number of iterative elongation steps and that shape the static architectural features responsible for organization of a water-mediated hydrogen bonding network necessary for termination of the elongation reaction by an intramolecular aldol cyclization and production of the 3,5-dihydroxybiphenyl BIS product. Elucidating these protein-substrate interactions provides a foundation for using polyketone CoA analogues to further unravel the control mechanisms of PKS catalysis and gain the insight necessary for predictive engineering of these enzymes.

PubMed: 40312803
DOI: 10.1021/jacs.5c05635

Experimental method

X-RAY DIFFRACTION (1.57 Å)