Study of the oxidative half-reaction catalyzed by a non-heme ferrous catalytic center by means of structural and computational methodologies
2007 (English)In: International Journal of Quantum Chemistry, ISSN 0020-7608, E-ISSN 1097-461X, Vol. 107, no 6, 1514-1522 p.Article in journal (Refereed) Published
Deacetoxycephalosporin C synthase (DAOCS) is a mononuclear ferrous enzyme that catalyzes the expansion of the five-membered thiazolidine ring of the penicillin nucleus into the six-membered dihydrothiazine ring of the cephalosporins. In the first half-reaction with dioxygen and 2-oxoglutarate, a reactive iron-oxygen species is produced that can subsequently react with the penicillin substrate to yield the cephalosporin. We describe quantum mechanical calculations of the first part of the reaction based on the high-resolution structures of the active site of DAOCS and its complexes with ligands. These studies are aimed at understanding how the reactive species can be produced and contained in the active site of the enzyme. The results demonstrate the priming of the active site by the co-substrate for oxygen binding and hint to the presence of a stable iron-peroxo intermediate in equilibrium with a more reactive ferryl species and the formation of CO2 as a leaving group by decarboxylation of 2-oxoglutarate. A conclusion from these studies is that substitution of CO2 by the penicillin substrate triggers the oxidation reaction in a booby-trap-like mechanism.
Place, publisher, year, edition, pages
2007. Vol. 107, no 6, 1514-1522 p.
mononuclear ferrous enzyme, deacetoxycephalosporin C synthase, ring expansion, density functional theory calculations, ab initio dynamics
IdentifiersURN: urn:nbn:se:uu:diva-150912DOI: 10.1002/qua.21275ISI: 000244771500027OAI: oai:DiVA.org:uu-150912DiVA: diva2:409291