The catalytic mechanism of a natural Diels–Alderase revealed in molecular detail

DOI: 10.1021/jacs.6b00232

Authors: Matthew J. Byrne (University of Bristol) , Nicholas R. Lees (University of Bristol) , Li-Chen Han (University of Bristol) , Marc W. Van Der Kamp (University of Bristol) , Adrian J. Mulholland (University of Bristol) , James E. M. Stach (Newcastle University) , Christine L. Willis (University of Bristol) , Paul R. Race (University of Bristol)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Journal Of The American Chemical Society , VOL 138 , PAGES 6095 - 6098

State: Published (Approved)
Published: May 2016
Diamond Proposal Number(s): 8922

Abstract: The Diels–Alder reaction, a [4 + 2] cycloaddition of a conjugated diene to a dienophile, is one of the most powerful reactions in synthetic chemistry. Biocatalysts capable of unlocking new and efficient Diels–Alder reactions would have major impact. Here we present a molecular-level description of the reaction mechanism of the spirotetronate cyclase AbyU, an enzyme shown here to be a bona fide natural Diels–Alderase. Using enzyme assays, X-ray crystal structures, and simulations of the reaction in the enzyme, we reveal how linear substrate chains are contorted within the AbyU active site to facilitate a transannular pericyclic reaction. This study provides compelling evidence for the existence of a natural enzyme evolved to catalyze a Diels–Alder reaction and shows how catalysis is achieved.

Journal Keywords: Peptides and proteins; Surface interactions; Cyclization; Crystal structure; Addition reactions

Diamond Keywords: Enzymes

Subject Areas: Biology and Bio-materials, Chemistry


Instruments: I04-1-Macromolecular Crystallography (fixed wavelength) , I24-Microfocus Macromolecular Crystallography

Added On: 24/04/2017 12:12

Discipline Tags:

Biotechnology Biochemistry Catalysis Chemistry Structural biology Engineering & Technology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)