{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Otten R"],"funding":["ETH Zürich Foundation","U.S. Department of Energy","Swiss National Science Foundation","Howard Hughes Medical Institute","BioXFEL Science and Technology Center","Damon Runyon Cancer Research Foundation","NIH HHS","NIGMS NIH HHS"],"pagination":["1442-1446"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9616100"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["370(6523)"],"pubmed_abstract":["The advent of biocatalysts designed computationally and optimized by laboratory evolution provides an opportunity to explore molecular strategies for augmenting catalytic function. Applying a suite of nuclear magnetic resonance, crystallography, and stopped-flow techniques to an enzyme designed for an elementary proton transfer reaction, we show how directed evolution gradually altered the conformational ensemble of the protein scaffold to populate a narrow, highly active conformational ensemble and accelerate this transformation by nearly nine orders of magnitude. Mutations acquired during optimization enabled global conformational changes, including high-energy backbone rearrangements, that cooperatively organized the catalytic base and oxyanion stabilizer, thus perfecting transition-sta"],"journal":["Science (New York, N.Y.)"],"pubmed_title":["How directed evolution reshapes the energy landscape in an enzyme to boost catalysis."],"pmcid":["PMC9616100"],"funding_grant_id":["P41 GM103393","1231306","DE-FG02-05ER15699","P30 GM124169","S10 OD021832","DRG-2114-12","T32 GM135126"],"pubmed_authors":["Padua RAP","Nguyen V","Sui S","Cohen AE","Bunzel HA","Otten R","Kern D","Pitsawong W","Perry SL","Hilvert D","Patterson M"],"additional_accession":[]},"is_claimable":false,"name":"How directed evolution reshapes the energy landscape in an enzyme to boost catalysis.","description":"The advent of biocatalysts designed computationally and optimized by laboratory evolution provides an opportunity to explore molecular strategies for augmenting catalytic function. Applying a suite of nuclear magnetic resonance, crystallography, and stopped-flow techniques to an enzyme designed for an elementary proton transfer reaction, we show how directed evolution gradually altered the conformational ensemble of the protein scaffold to populate a narrow, highly active conformational ensemble and accelerate this transformation by nearly nine orders of magnitude. Mutations acquired during optimization enabled global conformational changes, including high-energy backbone rearrangements, that cooperatively organized the catalytic base and oxyanion stabilizer, thus perfecting transition-sta","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020 Dec","modification":"2026-05-28T00:37:10.12Z","creation":"2025-04-06T21:03:48.735Z"},"accession":"S-EPMC9616100","cross_references":{"pubmed":["33214289"],"doi":["10.1126/science.abd3623"]}}