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Planta Med 2015; 81(06): 467-473
DOI: 10.1055/s-0035-1545697
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Similarity between Flavonoid Biosynthetic Enzymes and Flavonoid Protein Targets Captured by Three-Dimensional Computing Approach

Noé Sturm
1   Eskitis Institute for Drug Discovery, Griffith University, Brisbane, Australia
2   Laboratory of Therapeutic Innovation, Medalis Drug Discovery Center, Université de Strasbourg, Illkirch, France
,
Ronald J. Quinn
1   Eskitis Institute for Drug Discovery, Griffith University, Brisbane, Australia
,
Esther Kellenberger
2   Laboratory of Therapeutic Innovation, Medalis Drug Discovery Center, Université de Strasbourg, Illkirch, France
› Author Affiliations
Further Information

Publication History

received 06 July 2014
revised 19 January 2015

accepted 23 January 2015

Publication Date:
26 February 2015 (online)

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Abstract

Natural products are made by nature through interaction with biosynthetic enzymes. They also exert their effect as drugs by interaction with proteins. To address the question “Do biosynthetic enzymes and therapeutic targets share common mechanisms for the molecular recognition of natural products?”, we compared the active site of five flavonoid biosynthetic enzymes to 8077 ligandable binding sites in the Protein Data Bank using two three-dimensional-based methods (SiteAlign and Shaper). Virtual screenings efficiently retrieved known flavonoid targets, in particular protein kinases. A consistent performance obtained for variable site descriptions (presence/absence of water, variable boundaries, or small structural changes) indicated that the methods are robust and thus well suited for the identification of potential target proteins of natural products. Finally, our results suggested that flavonoid binding is not primarily driven by shape, but rather by the recognition of common anchoring points.

Key words

flavonoid - biosynthetic enzyme - natural product - binding site similarity

Supporting Information

 

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