Quantum chemical modeling of enzymatic reactions: the case of 4-oxalocrotonate tautomerase
2007 (English)In: Bioorganic chemistry (Print), ISSN 0045-2068, E-ISSN 1090-2120, Vol. 35, no 6, 444-457 p.Article in journal (Refereed) Published
The reaction mechanism of 4-oxalocrotonate tautomerase (4-OT) is studied using the density functional theory method B3LYP. This enzyme catalyzes the isomerisation of unconjugated alpha-keto acids to their conjugated isomers. Two different quantum chemical models of the active site are devised and the potential energy curves for the reaction are computed. The calculations support the proposed reaction mechanism in which Pro-1 acts as a base to shuttle a proton from the C3 to the C5 position of the substrate. The first step (proton transfer from C3 to proline) is shown to be the rate-limiting step. The energy of the charge-separated intermediate (protonated proline-deprotonated substrate) is calculated to be quite low, in accordance with measured pK(a) values. The results of the two models are used to evaluate the methodology employed in modeling enzyme active sites using quantum chemical cluster models.
Place, publisher, year, edition, pages
2007. Vol. 35, no 6, 444-457 p.
4-oxalocrotonate tautomerase, density functional theory, reaction mechanism
IdentifiersURN: urn:nbn:se:kth:diva-8244DOI: 10.1016/j.bioorg.2007.08.003ISI: 000251363100003ScopusID: 2-s2.0-35448993293OAI: oai:DiVA.org:kth-8244DiVA: diva2:13514
QC 20100928. Uppdaterad från Accepted till Published (20100928).2008-04-222008-04-222010-11-23Bibliographically approved