Licentiate Thesis

Mechanistic Insights into Dinuclear Zinc Enzymes from Density Functional Theory Studies

Defence

Defendant: Rong-Zhen Liao

Time: Friday 2009-04-24, 14:00

Place: FB52, AlbaNova

Opponents: Dr. Lubomir Rulisek, Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Praha, Czech Republic and Prof. Margareta Blomberg, Department of Physics, Stockholm University, Stockholm

Supervisor: Dr. Fahmi Himo

Abstract

Quantum chemical methods have been used to shed light on the reaction mechanisms of several dinuclear zinc enzymes. The enzymes studied are involved in the hydrolysis of phosphates, amides, and carboxylic esters, namely RNase Z, Dihydroorotase (DHO), and N-acyl homoserine lactone hydrolase (AHL lactonase). The density functional method B3LYP, together with quite large active site models, was used to investigate these enzymatic reactions. Several plausible proposed mechanisms, involving protonation states of important active site residues (DHO), substrate orientations (AHL lactonase), have been considered. The calculated energetics can be used to assess the feasibility of the suggested reaction mechanisms. Based on the calculations and also on other related dinuclear zinc enzymes studied previously, some general mechanistic features have been uncovered.

2009, ISBN 978-91-7415-261-6

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