2026-04-13T02:57:54Zhttps://recercat.cat/oai/request

oai:recercat.cat:10256/138622024-10-29T23:14:54Zcom_2072_452955com_2072_2054col_2072_453073

Exploring the reversal of enantioselectivity on a Zinc-dependent Alcohol Dehydrogenase Maria Solano, Miguel A. Romero Rivera, Adrian Osuna Oliveras, Sílvia Ministerio de Economía y Competitividad (Espanya) Enzims Enzymes Catàlisi Catalysis Dinàmica molecular Molecular dynamics Alcohol Dehydrogenase (ADH) enzymes catalyse the reversible reduction of prochiral ketones to the corresponding alcohols. These enzymes present two differently shaped active site pockets, which dictate their substrate scope and selectivity. In this study, we computationally evaluate the effect of two commonly reported active site mutations (I86A, and W110T) on a secondary alcohol dehydrogenase from Thermoanaerobacter brockii (TbSADH) through Molecular Dynamics simulations. Our results indicate that the introduced mutations induce dramatic changes on the shape of the active site, but most importantly they impact the substrate-enzyme interactions. We demonstrate that the combination of Molecular Dynamics simulations with the tools POVME and NCIplot correspond to a powerful strategy for rationalising and engineering the stereoselectivity of ADH variants A.R.R. thanks the Generalitat de Catalunya for PhD fellowship (2015-FI-B-00165), M.A.M.S is grateful to the Spanish MINECO for PhD fellowship (BES-2015-074964). S.O. thanks the Spanish MINECO for project CTQ2014-59212-P, Ramón y Cajal contract (RYC-2014-16846), the European Community for CIG project (PCIG14-GA-2013-630978), and the funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (ERC-2015-StG-679001) 2017-04-18 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://hdl.handle.net/10256/13862 eng info:eu-repo/semantics/altIdentifier/doi/10.1039/C7OB00482F info:eu-repo/semantics/altIdentifier/issn/1477-0520 info:eu-repo/semantics/altIdentifier/eissn/1477-0539 info:eu-repo/grantAgreement/MINECO//CTQ2014-59212-P/ES/SPIN STATE AND ENZYMATIC CATALYSIS BASED ON BOTTOM-UP COMPUTATIONAL DESIGN/ info:eu-repo/grantAgreement/EC/FP7/630978/EU/Computational Exploration of Directed Evolution rules for tuning enzymatic activities/DIREVENZYME info:eu-repo/grantAgreement/EC/H2020/679001/EU/Network models for the computational design of proficient enzymes/NetMoDEzyme Attribution-NonCommercial 3.0 Spain http://creativecommons.org/licenses/by-nc/3.0/es/ info:eu-repo/semantics/openAccess application/pdf Royal Society of Chemistry (RSC) Organic and Biomolecular Chemistry, 2017, vol. 15, núm. 19, p. 4122-4129 Articles publicats (D-Q)