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Mutagenesis Study of Active Site Residues in Chorismate Mutase from Helicobacter pylori strain 26695
Thesis

Mutagenesis Study of Active Site Residues in Chorismate Mutase from Helicobacter pylori strain 26695

Chia-Chi Lin
Masters, 國立清華大學, 生物資訊與結構生物研究所
2004

Abstract

分枝酸變位酵素 莽草酸途徑 胃幽門桿菌 定點突變 活性區 Chorismate mutase shikimate pathway Helicobacter pylori mutagenesis active-site residues
Helicobacter pylori (H. pylori), a gram-negative, spiral-shaped and flagellated organism, colonized the gastric mucosa and significantly involved the cause of gastric ulcers and gastric cancers. The whole genome sequences of H. pylori strain 26695 have been reported in 1997. The HP0291 gene, encoding the chorismate mutase (CM), is a key enzyme of the shikimate pathway to the synthesis of aromatic amino acids. HP0291, which belongs to a monofunctional AroQ class of CMs, catalyzes the conversion of chorismate to prephenate. Based on the computational analysis of HP0291 protein sequence and 3-Dimensional structure, it suggests that Arg13, Arg30, Lys41, Cys48, Arg51, Glu52, Ile55, Phe80, Ser83 and Gln87 might be the active-site residues. Fourteen site-directed mutants of each residue have been constructed to test their structural and functional role. Although protein structure and stability of these mutants were similar to that of wild-type protein, most of the mutants showed 80-90% loss of their enzyme activities. Our results demonstrated that Arg13, Lys41, Cys48, Arg51, Glu52, Ile55, Phe80 and Gln87 were critical to the HP0291 functions.

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