Volume 1356, Issue 2 (No.1-111 1977)                   1977, 1356(2): 2-3 | Back to browse issues page

XML Persian Abstract Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

noohi B, Zahedi M, Ghiasi M. Theoritical study on the catalytic and inhibition mechanism of the β-lactam antibiotics by metallo-β-lactamases in the different solvents and different temperatures by using quantum mechanical calculations. Quarterly Journal of Science Kharazmi University. 1977; 1356 (2) :2-3
URL: http://jsci.khu.ac.ir/article-1-1947-en.html
Abstract:   (4152 Views)
The most prevalent and important mechanism of bacterial resistance to &beta-lactam antibiotics, is the production of &beta-lactamase enzymes which inactivate these drugs by the hydrolytic cleavage of the four-membered &beta-lactam ring during two steps which is including the nucleophilic attack of the bridging hydroxide ion on the substrate and eventual protonation of the leaving amine group. During this reaction, metal ions play an important role in the catalytic process. Despite the availability of &beta-lactamase crystallographic structures, their mechanism of action is still unclear and no clinically useful inhibitors of these enzymes have been reported. Density functional theory (DFT) using B3LYP and 6-31G, 6-31G* and 6-311G** basis sets have been employed to calculate the details of electronic structure and electronic energy of catalytic reaction of CcrA enzyme active center from metallo-&beta-lactamase enzymes (M&betaLs), penicillin from &beta-lactam antibiotics, and the formed complexes including ES, ETS1, EI1, EI2, ETS2 and EP respectively, has been used. Also all the thermodynamic functions including ∆Hº, ∆Sº and ∆Gº to form two transition states, ETS1 and ETS2, and for the total reaction are evaluated at 25 °C, 31 °C, 37 °C and 40 °C and 1 atmosphere pressure. In all calculations solvent effects have been considered by using PCM method for water, ethanol, protein environment, nitro methane and carbon tetrachloride. Finally this reaction proceeds during an exothermic and spontaneous process, and the first step, the nucleophilic attack of the bridging hydroxide ion on the substrate, is the rate-limiting step
Type of Study: S |
Published: 1977/08/15

Add your comments about this article : Your username or Email:

Send email to the article author

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

© 2022 CC BY-NC 4.0 | Quarterly Journal of Science Kharazmi University

Designed & Developed by : Yektaweb