Amidases Have a Hydrogen Bond that Facilitates Nitrogen Inversion, but Esterases Have Not
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...
| Published in: | ChemCatChem |
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| Main Authors: | , |
| Format: | Article in Journal/Newspaper |
| Language: | English |
| Published: |
Wiley
2011
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| Subjects: | |
| Online Access: | http://dx.doi.org/10.1002/cctc.201000448 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fcctc.201000448 http://onlinelibrary.wiley.com/wol1/doi/10.1002/cctc.201000448/fullpdf |
| Summary: | 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. |
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