Theoretical Study of the Phosphotriesterase Reaction Mechanism
2007 (English)In: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 111, no 6, 1253-1255 p.Article in journal (Refereed) Published
Phosphotriesterase (PTE) is a binuclear zinc enzyme that catalyzes the hydrolysis of extremely toxic organophosphate triesters. In the present work, we have investigated the reaction mechanism of PTE using the hybrid density functional theory method B3LYP. We present a potential energy surface for the reaction and provide characterization of the transition states and intermediates. We used the high resolution crystal structure to construct a model of the active site of PTE, containing the two zinc ions and their first shell ligands. The calculations provide strong support to an associative mechanism for the hydrolysis of phosphotriesters by PTE. No protonation of the leaving group was found to be necessary. In particular, the calculations demonstrate that the nucleophilicity of the bridging hydroxide is sufficient to be utilized in the hydrolysis reaction, a feature that is of importance for a number of other di-zinc enzymes.
Place, publisher, year, edition, pages
2007. Vol. 111, no 6, 1253-1255 p.
BACTERIAL PHOSPHOTRIESTERASE; ACTIVE-SITE; 3-DIMENSIONAL STRUCTURE; PSEUDOMONAS-DIMINUTA; DENSITY; HYDROLYSIS; ENERGY; MODEL; BINUCLEAR; ALKALINE
IdentifiersURN: urn:nbn:se:kth:diva-9747DOI: 10.1021/jp068500nISI: 000244039700002ScopusID: 2-s2.0-33847410577OAI: oai:DiVA.org:kth-9747DiVA: diva2:127405
QC 201007142008-12-052008-12-052010-07-14Bibliographically approved