Computational Design of an Enzyme Catalyst for a Stereoselective Bimolecular Diels-Alder Reaction
Top Cited Papers
- 16 July 2010
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 329 (5989), 309-313
- https://doi.org/10.1126/science.1190239
Abstract
The Diels-Alder reaction is a cornerstone in organic synthesis, forming two carbon-carbon bonds and up to four new stereogenic centers in one step. No naturally occurring enzymes have been shown to catalyze bimolecular Diels-Alder reactions. We describe the de novo computational design and experimental characterization of enzymes catalyzing a bimolecular Diels-Alder reaction with high stereoselectivity and substrate specificity. X-ray crystallography confirms that the structure matches the design for the most active of the enzymes, and binding site substitutions reprogram the substrate specificity. Designed stereoselective catalysts for carbon-carbon bond-forming reactions should be broadly useful in synthetic chemistry.Keywords
This publication has 13 references indexed in Scilit:
- The Putative Diels−Alderase Macrophomate Synthase is an Efficient AldolaseJournal of the American Chemical Society, 2008
- Kemp elimination catalysts by computational enzyme designNature, 2008
- De Novo Computational Design of Retro-Aldol EnzymesScience, 2008
- New algorithms and an in silico benchmark for computational enzyme designProtein Science, 2006
- Insight into a natural Diels–Alder reaction from the structure of macrophomate synthaseNature, 2003
- The Origins of Noncovalent Catalysis of Intermolecular Diels−Alder Reactions by Cyclodextrins, Self-Assembling Capsules, Antibodies, and RNAsesThe Journal of Organic Chemistry, 2002
- Native protein sequences are close to optimal for their structuresProceedings of the National Academy of Sciences of the United States of America, 2000
- Enhanced Hydrogen Bonding of Water to Diels-Alder Transition States. Ab Initio EvidenceThe Journal of Organic Chemistry, 1994
- Control of the exo and endo Pathways of the Diels-Alder Reaction by Antibody CatalysisScience, 1993
- Entropic Contributions to Rate Accelerations in Enzymic and Intramolecular Reactions and the Chelate EffectProceedings of the National Academy of Sciences of the United States of America, 1971