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Functional interaction of diphenols with polyphenol oxidase. Molecular determinants of substrate/inhibitor specificity.

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FEBS-02-07
 
Title Functional interaction of diphenols with polyphenol oxidase. Molecular determinants of substrate/inhibitor specificity.
 
Creator Kanade, Santosh R
Suhas, V L
Chandra, Nagasuma
Gowda, Lalitha R
 
Subject 23 Vegetables
16 Enzyme Chemistry
 
Description 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 coordinates of the trigonal pyramidal coordination polyhedron of CuA. The spatial orientation of the hydroxyl in relation to the carboxylic group either allows a perfect fit in the substrate cavity, leading to inhibition, or because of a steric clash flips the molecule vertically, facilitating oxidation. This is the first study to explain, at the molecular level, the determinants of substrate and inhibitor specificity of a catechol oxidase, thereby providing a platform for the design of selective inhibitors useful to both the food and pharmaceutical industries.
 
Date 2007
 
Type Article
PeerReviewed
 
Format application/pdf
 
Language en
 
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Identifier http://ir.cftri.com/1850/1/FEBS_Journal_274%2816%29_2007_4177-4187.pdf
Kanade, Santosh R and Suhas, V L and Chandra, Nagasuma and Gowda, Lalitha R (2007) Functional interaction of diphenols with polyphenol oxidase. Molecular determinants of substrate/inhibitor specificity. The FEBS journal, 274 (16). pp. 4177-87. ISSN 1742-464X