We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Amidases Have a Hydrogen Bond that Facilitates Nitrogen Inversion, but Esterases Have Not.
- Authors
Syrén, Per-Olof; Hult, Karl
- Abstract
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. By using molecular modeling we found a hydrogen bond donated by the scissile NH-group of the peptide substrate in the transition state facilitating nitrogen inversion in the active site of amidases. The interaction, which is missing in esterases, was found in sixteen analyzed amidases representing ten different reaction mechanisms and eleven folding families.
- Publication
ChemCatChem, 2011, Vol 3, Issue 5, p853
- ISSN
1867-3880
- Publication type
Article
- DOI
10.1002/cctc.201000448