ENZYMATIC MECHANISMS OF P CRESOL METHYLHYDROXYLASE &COVALENT FLAVIN ATTACHMENT

$136P41FY2000RRNIH

University Of California San Francisco, San Francisco CA

Investigators

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Abstract

The enzyme P-Cresol-methylhydroxylase is a flacocytochrome and catalyzes the oxidation of p-cresol to 4-hydroxybenzylalcohol. In a second step 4-hydroxybenzylalcohol is further oxidized to the final product 4-hydroxybenzaldehyde. The enzymological and biochemical studies I have planned revolve around 1) the molecular mechanism of covalent FAD attachment, which was shown in the past to be an autocatalytic process; and, 2) the enzymatic mechanism of p-cresol and p-hydroxybenzylalcohol oxidation. Experimental design and interpretation of data in both projects rely strongly on several three dimensional structures of the enzyme which are now available from x-ray crystallographic studies. Inspection and analysis of the structures will be performed in the Computer Graphics Laboratory using MidasPlus.

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