Novel Approach for Identifying Key Residues in Enzymatic Reactions: Proton Abstraction in Ketosterbid Isomerase
2014 (English)In: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 118, no 46, 13050-13058 p.Article in journal (Refereed) Published
We propose a computationally efficient approach for evaluating the individual contributions of many different residues to the catalytic efficiency of an enzymatic reaction. This approach is based on the fragment molecular orbital (FMO) method, and it defines the energy of a deletion form, i.e., the energy of the system when a particular residue is deleted. Using this approach, we found that, among 10 investigated residues, three, Tyr14, Asp99, and Tyr55, in this order, significantly reduce the activation energy of the proton abstraction from a substrate, cyclopent-2-enone, catalyzed by ketosteroid isomerase (KSI). The relative activation energies estimated in this study are in good agreement with available previous experimental and theoretical data obtained for the similar proton abstraction with a native substrate and substitution mutants of KSI. It was thus indicated that the new approach is efficient for rationally evaluating the catalytic effects of multiple residues on an enzymatic reaction.
Place, publisher, year, edition, pages
American Chemical Society (ACS), 2014. Vol. 118, no 46, 13050-13058 p.
Enzyme design, enzymatic catalysis, fragment molecular orbital method, deletion form, activation energy
IdentifiersURN: urn:nbn:se:kth:diva-158400DOI: 10.1021/jp508423sISI: 000345468600003ScopusID: 2-s2.0-84912141064OAI: oai:DiVA.org:kth-158400DiVA: diva2:778158
QC 201501092015-01-092015-01-072015-04-24Bibliographically approved