The modelling and kinetic investigation of the lipase-catalysed acetylation of stereoisomeric prostaglandins
2005 (English)In: Journal of Molecular Catalysis B: Enzymatic, ISSN 1381-1177, Vol. 35, no 1-3, 62-69 p.Article in journal (Refereed) Published
The lipase-catalysed acetylation of the hydroxyl groups of five stereoisomeric prostaglandins of type F was investigated by means of molecular dynamics simulations and the results compared with experimental observations. An NMR spectroscopic monitoring was performed to estimate reaction velocities and the regioselectivity. A molecular modelling protocol that could qualitatively differentiate between the OH groups of prostaglandins being either accessible or unaccessible to the Candida antarctica lipase B (CALB) catalysed acetylation was developed. The protocol developed analysed the protein structure deformation, the content of essential hydrogen bonds and the function-based subset energy of tetrahedral intermediates along the molecular dynamics simulations trajectory. The tetrahedral intermediates displaying a deformation RMS value lower than 3.0 angstrom, an essential hydrogen bond content over 50% and a subset energy less than -95 kJ/mol were classified active. In total, the accessibility of 16 out of 17 different prostaglandin OH groups was correctly predicted.
Place, publisher, year, edition, pages
2005. Vol. 35, no 1-3, 62-69 p.
lipase-catalysed acetylation, Novozym 435, low-water media, monitoring by H-1 NMR, prostaglandin, molecular dynamics simulations, enantiomerically pure diastereomers, candida-antarctica, nucleic-acids, force-field, isoprostanes, physiology, proteins, ester
Biochemistry and Molecular Biology
IdentifiersURN: urn:nbn:se:kth:diva-14929DOI: 10.1016/j.molcatb.2005.05.008ISI: 000230671100011ScopusID: 2-s2.0-21644442447OAI: oai:DiVA.org:kth-14929DiVA: diva2:332970
QC 201005252010-08-052010-08-052011-01-24Bibliographically approved