On the observation of a gem diol intermediate after O-O bond cleavage by extradiol dioxygenases. A hybrid DFT study
2010 (English)In: Journal of Molecular Modeling, ISSN 1610-2940, E-ISSN 0948-5023, Vol. 16, no 11, 1673-1677 p.Article in journal (Refereed) Published
Catalytic cycle intermediates of a representative extradiol dioxygenase, homoprotocatechuate 2,3-dioxygenase (HPCD), have recently been characterized in crystallo by Kovaleva and Lipscomb. The structures of the identified species indicate that the process of inserting oxygen into the catechol ring occurs stepwise, and involves an Fe(II)-alkylperoxo intermediate and its O-O cleavage product: a gem diol species. In general, these findings corroborate the results of our previous computational studies; however, the fact that the gem diol species is stable enough to be observed in the crystal form seems to be at odds with the computational mechanistic data, which suggest that this intermediate should very readily and spontaneously convert to the epoxide species. The key question then becomes what is actually observed in the X-ray experiments. Here we report additional computational studies undertaken with the hope of clarifying this issue. The results obtained for active site models hosting both the native and the alternative (4-sulfonylcatechol) substrate indicate that the stability of the gem diol species is substantially increased if an electron and a proton are added. If this occurs somehow, the lifetime of the intermediate should be sufficient to observe it.
Place, publisher, year, edition, pages
2010. Vol. 16, no 11, 1673-1677 p.
Homoprotocatechuate 2, 3-dioxygenase, Extradiol, Ring cleavage, Density functional calculations
IdentifiersURN: urn:nbn:se:su:diva-66233DOI: 10.1007/s00894-010-0652-5ISI: 000282515400002OAI: oai:DiVA.org:su-66233DiVA: diva2:467605
authorCount :32011-12-192011-12-192011-12-19Bibliographically approved