Amidases have a hydrogen bond that facilitates nitrogen inversion but esterases have not
2011 (English)In: ChemCatChem, ISSN 1867-3899, Vol. 3, no 5, 853-860 p.Article in journal (Refereed) Published
The fact that proteases/amidases can hydrolyze amides efficiently whereas esterases can not has been discussed during the last decades. By using molecular modeling we have found a hydrogen bond in the transition state for protease/amidase catalyzed hydrolysis of peptides and amides donated by the scissile NH-group of the substrate. The hydrogen-bond acceptor was found either in the enzyme (enzyme assisted) or in the substrate (substrate assisted). This new interaction with the NH-hydrogen in the transition state (TS) was found in sixteen proteases/amidases, which represent ten different reaction mechanisms and eleven different folding families. Esterases lack this interaction and, therefore, they are slow in hydrolyzing amides. By mimicking the substrate-assisted catalysis found in amidases we were able to shift reaction specificity of amide over ester synthesis of Candida antarctica lipase B one hundred fold. We propose that the hydrogen bond facilitates nitrogen inversion in amidases.
Place, publisher, year, edition, pages
2011. Vol. 3, no 5, 853-860 p.
Biochemistry and Molecular Biology
IdentifiersURN: urn:nbn:se:kth:diva-33330DOI: 10.1002/cctc.201000448ISI: 000290445100008ScopusID: 2-s2.0-80051810428OAI: oai:DiVA.org:kth-33330DiVA: diva2:414465
QC 201106082011-05-032011-05-032011-06-08Bibliographically approved