Author

Kenneth Wang

Date of Award

2014

Document Type

Thesis

Degree Name

Bachelors

Department

Natural Sciences

First Advisor

Shipman, Steven

Keywords

Enzymes, Catalysis, B-lactamase, Chemistry

Area of Concentration

Chemistry

Abstract

Molecular dynamics have been carried out on b-lactamase CTX-M structures resolved by the Chen group at USF. Several protonation states of CTX-M were set up using the CHARMM simulation package in order to mimic the hydrolysis mechanism upon ligand binding. 11 ns simulations show a short intermolecular hydrogen bond between the catalytic triad Serine and Lysine in probable states. Aspartate residues outside of the active site also show evidence of an intermolecular short hydrogen bond, which may play a role in overall protein stability. These results support the proposed mechanism of ligand induced low barrier hydrogen bond formation by Cleland and Kreevoy. These results further validate the role of short intermolecular hydrogen bonds in protein catalysis.

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