Theoretical Investigation of the Second-Shell Mechanism of Nitrile Hydratase
2008 (English)In: European Journal of Inorganic Chemistry, ISSN 1434-1948, E-ISSN 1099-0682, no 9, 1406-1412 p.Article in journal (Refereed) Published
Nitrile hydratases (NHases) are biocatalytically important enzymes that are utilized in the industrial production of acrylamide and nicotinamide. There are two different classes of NHases, harbouring either a low-spin Fe-III or a low-spin Co-III ion in the active site, in each case with the same peculiar set of ligands, involving deprotonated backbone amides and oxidized cysteine residues. The detailed reaction mechanism of NHase has not been established yet, but different proposals have been put forward. Depending on the binding site of the substrate, these can be divided into first-shell and second-shell mechanisms, respectively, Recently, we have investigated different first-shell mechanisms using quantum-chemical active-site models based on the iron-dependent NHase (Inorg. Chem. 2007, 46, 4850). Here we continue our investigation of the NHase reaction by exploring two different variations of the second-shell mechanism of the iron-dependent NHase. In the first, a metal-bound hydroxide ion performs a nucleophilic attack on the nitrile substrate, while in the second investigated mechanism, the oxidized cysteine, Cys114-SO-, acts as the nucleophile. We report energies, optimized transition state, and intermediate geometries for both investigated mechanisms. The calculated barriers are similar to the previously reported first-shell mechanism involving Cys114-SO- as catalytic base.
Place, publisher, year, edition, pages
2008. no 9, 1406-1412 p.
nitrile hydratase; enzyme catalysis; density functional theory; reaction mechanism
IdentifiersURN: urn:nbn:se:kth:diva-8109DOI: 10.1002/ejic.200701137ISI: 000254555300007ScopusID: 2-s2.0-53249107748OAI: oai:DiVA.org:kth-8109DiVA: diva2:13340
QC 20100811. Uppdaterad från in press till published (20100811).2008-03-182008-03-182010-08-11Bibliographically approved