Journal
JOURNAL OF MOLECULAR STRUCTURE-THEOCHEM
Volume 898, Issue 1-3, Pages 106-114Publisher
ELSEVIER
DOI: 10.1016/j.theochem.2008.06.033
Keywords
QM/MM calculations; Enzyme reaction mechanisms; Density functional theory; Reaction paths
Categories
Funding
- Eusko Jaurlaritza
- MEC
- EPSRC
- Engineering and Physical Sciences Research Council [EP/C532910/1] Funding Source: researchfish
- EPSRC [EP/J010588/1] Funding Source: UKRI
Ask authors/readers for more resources
Density functional theory-based QM/MM calculations (B3LYP/CHARMM27) are reported on a reaction path for the initial, rate-limiting, step in amide hydrolysis by Carboxypeptidase A. Obtaining a smooth energy profile with the QM/MM method for this system is difficult, and great care is needed in selecting the initial geometry and the method for optimising the reaction path. The calculations show the importance of the enzyme in stabilizing the tetrahedral intermediate, and suggest that the key step involves simultaneous deprotonation of the nucleophilic water, attack on the substrate carbonyl group, and protonation of the substrate amide nitrogen. (C) 2008 Elsevier B.V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available