Structural, mutational and kinetic analyses of Aquifex aeolicus prephenate dehydrogenase: Elucidation of the catalytic mechanism.
Published: 2006
Language: eng
Number of pages: 104
ISBN-13: 9780494211656
Description: Using the crystal structures as guides, active site residues were targeted for site-directed mutagenesis. Kinetic analyses of these variants combined with structural analyses indicate that Ser126 facilitates catalysis by coordinating the prephenate-His147-NAD+ interaction and hydrogen bonding to prephenate via the 4-hydroxyl group, while a gated mechanism consisting of Glu153-Arg250-Asp' modulates substrate access to the active site.Prephenate dehydrogenase, a member of the TyrA family, participates in tyrosine biosynthesis by catalyzing the oxidative decarboxylation of prephenate to 4-hydroxyphenylpyruvate in the presence of NAD+. The current study attempts to elucidate the catalytic mechanism of this enzyme through structural and mutational approaches.Aquifex aeolicus prephenate dehydrogenase was co-crystallized with NAD+, NAD+ and tyrosine, and NAD + and 4-hydroxyphenylpropionate. These crystal structures provide positional information on known active site residues and reveal the interactions between enzyme and substrate.The results presented from this study provide a framework for understanding the mechanism of substrate discrimination within the TyrA family.
Notes: Source: Masters Abstracts International, Volume: 45-03, page: 1391.

Thesis (M.Sc.)--University of Toronto, 2006.

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