Do they make a good match? Molecular dynamics studies on CALB-catalyzed esterification of 3-phenylpropionic and cinnamic acids

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• dc.contributor.author Zieniuk, Bartlomiej
• dc.contributor.author Stepniewski, Tomasz Maciej, 1988-
• dc.contributor.author Fabiszewska, Agata
• dc.date.accessioned 2024-10-01T06:31:41Z
• dc.date.available 2024-10-01T06:31:41Z
• dc.date.issued 2023
• dc.description.abstract Lipases are versatile catalysts widely used in industrial biotransformations and laboratory-scale developed reactions with industrial potential. Despite the fact that lipase B from Candida antarctica (CALB) is one of the most widely used lipolytic enzymes, its substrate specificity is still poorly understood. One observed trend is that reactions carried out with carboxylic acids containing a double bond are less efficient on average. Here, we have utilized a combination of in vitro and in silico techniques, to better understand the negative impact of a double bond on CALB-mediated esterification. Then through extensive molecular dynamics (MD) simulations, we were able to map the entry pathway of cinnamic acid and its derivative into the CALB active site, and their interactions with catalytic residues. We observed a 2 step binding mechanism of studied compounds, where they first penetrate the enzyme pocket in a conformation where their carboxylic groups are extended towards the solvent. This is followed by further penetration of the acid into the enzymatic active pocket, and a full rotation within the active site, which orients the acid in a conformation that allows further steps of the esterification reaction. As acids containing a double bond are more rigid, their mobility and thus ability to rotate in the narrow CALB active site is hampered, which provides a structural explanation for the decreased efficiency of such acids. Our data provide insight into the substrate specificity of CALB-mediated esterification, providing important structural guidelines to better understand and potentially improve the efficiency of such reactions.
• dc.format.mimetype application/pdf
• dc.identifier.citation Zieniuk B, Stępniewski TM, Fabiszewska A. Do they make a good match? Molecular dynamics studies on CALB-catalyzed esterification of 3-phenylpropionic and cinnamic acids. Arch Biochem Biophys. 2023 Dec;750:109807. DOI: 10.1016/j.abb.2023.109807
• dc.identifier.doi http://dx.doi.org/10.1016/j.abb.2023.109807
• dc.identifier.issn 0003-9861
• dc.identifier.uri http://hdl.handle.net/10230/61275
• dc.language.iso eng
• dc.publisher Elsevier
• dc.relation.ispartof Arch Biochem Biophys. 2023 Dec;750:109807
• dc.rights © 2023 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC license (http://creativecommons.org/licenses/by-nc/4.0/).
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by-nc/4.0/
• dc.subject.keyword 3-Phenylpropionic acid
• dc.subject.keyword C. antarctica lipase B
• dc.subject.keyword Cinnamic acid
• dc.subject.keyword Enzyme substrate specificity
• dc.subject.keyword Esterification
• dc.subject.keyword Molecular dynamics
• dc.subject.keyword Novozym 435
• dc.title Do they make a good match? Molecular dynamics studies on CALB-catalyzed esterification of 3-phenylpropionic and cinnamic acids
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion