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Forward Kinetic Assay of Phosphopantetheine Adenylyltransferase from Helicobacter pylori and Its Critical Residue Mutants
Thesis

Forward Kinetic Assay of Phosphopantetheine Adenylyltransferase from Helicobacter pylori and Its Critical Residue Mutants

Hsieh, Chia-Chan
Masters, 國立清華大學, 生物資訊與結構生物研究所
2011

Abstract

磷酸泛酸醯基乙胺腺苷轉移酶 胃幽門螺旋桿菌 Phosphopantetheine Adenylyltransferase Helicobacter pylori
H. pylori is a gram-negative and microaerophilic bacterium found in human stomach. It infects more than 50% of the world population and increases the risk of developing gastric ulcer and stomach cancer. The standard first-line is a one week “triple therapy” but an increasing number of infected individuals are found to harbor antibiotic-resistant bacteria. It is important to find a new treatment or antibacterial drug targets to H. pylori. Coenzyme A (CoA) biosynthesis pathway is a good antimicrobial drug target to inhibit H. pylori infection because Coenzyme A is an essential cofactor in synthesis of oxidation of fatty acid for all living organisms. Phosphopantetheine adenylyltransferase (PPAT) is the rate-limiting enzyme involved in this pathway. Understanding the PPAT catalytic mechanism is important for drugs design. The structure of H. pylori PPAT has been determined recently. I had used the site-directed mutagenesis to identify the critical residues take part in enzyme catalysis by kinetic analysis. It provided important information about those critical residues when designing drugs.

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