tailieunhanh - Báo cáo khoa học: Functional interaction of diphenols with polyphenol oxidase

Polyphenol oxidase (PPO) catalyzes the oxidation ofo-diphenols to their respective quinones. The quinones autopolymerize to form dark pigments, an undesired effect. PPO is therefore the target for the development of antibrowning and antimelanization agents. A series of phenolic compounds experimentally evaluated for their binding affinity and inhibition constants were computationally docked to the active site of catechol oxidase. | ỊFEBS Journal Functional interaction of diphenols with polyphenol oxidase Molecular determinants of substrate inhibitor specificity Santosh R. Kanade1 V. L. Suhas2 Nagasuma Chandra2 and Lalitha R. Gowda1 1 Department of Protein Chemistry and Technology CentralFood TechnologicalResearch Institute Mysore India 2 Bioinformatics Centre Indian Institute of Science Bangalore India Keywords autodock computationalmodeling catechol oxidase enzyme mechanism field bean Dolichos lablab phenolic substrate inhibitor Correspondence L. R. Gowda Department of Protein Chemistry and Technology CentralFood Technological Research Institute Mysore 570 020 India Fax 91 821 251 7233 Tel 91 821 251 5331 E-mail lrg@ Received 22 April2007 revised 23 May 2007 accepted 15 June 2007 doi Polyphenol oxidase PPO catalyzes the oxidation of o-diphenols to their respective quinones. The quinones autopolymerize to form dark pigments an undesired effect. PPO is therefore the target for the development of antibrowning and antimelanization agents. A series of phenolic compounds experimentally evaluated for their binding affinity and inhibition constants were computationally docked to the active site of catechol oxidase. Docking studies suggested two distinct modes of binding dividing the docked ligands into two groups. Remarkably the first group corresponds to ligands determined to be substrates and the second group corresponds to reversible inhibitors. Analyses of the complexes provide structural explanations for correlating subtle changes in the position and nature of the substitutions on diphenols to their functional properties as substrates and inhibitors. Higher reaction rates and binding are reckoned by additional interactions of the substrates with key residues that line the hydrophobic cavity. The docking results suggest that inhibition of oxidation stems from an interaction between the aromatic carboxylic acid group and the apical His109 of the four .