Abstract
YopH plays a relevant role in three pathogenic species of Yersinia. Due to its importance in the prevention of the inflammatory response of the host, this enzyme has become a valid target for the identification and development of new inhibitors. In this work, an in-house library of 283 synthetic compounds was assayed against recombinant YopH from Yersinia enterocolitica. From these, four chalcone derivatives and one sulfonamide were identified for the first time as competitive inhibitors of YopH with binding affinity in the low micromolar range. Molecular modeling investigations indicated that the new inhibitors showed similar binding modes, establishing polar and hydrophobic contacts with key residues of the YopH binding site.
Copyright © 2013 Elsevier Masson SAS. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Bacterial Outer Membrane Proteins / antagonists & inhibitors*
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Bacterial Outer Membrane Proteins / isolation & purification
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Bacterial Outer Membrane Proteins / metabolism
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Chalcones / chemical synthesis*
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Chalcones / chemistry
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Chalcones / pharmacology*
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Dose-Response Relationship, Drug
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology*
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Kinetics
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Models, Molecular
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Molecular Structure
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Protein Tyrosine Phosphatases / antagonists & inhibitors*
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Protein Tyrosine Phosphatases / isolation & purification
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Protein Tyrosine Phosphatases / metabolism
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Recombinant Proteins / antagonists & inhibitors
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Recombinant Proteins / isolation & purification
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Recombinant Proteins / metabolism
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Structure-Activity Relationship
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Sulfonamides / chemical synthesis*
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Sulfonamides / chemistry
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Sulfonamides / pharmacology*
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Yersinia enterocolitica / enzymology*
Substances
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Bacterial Outer Membrane Proteins
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Chalcones
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Enzyme Inhibitors
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Recombinant Proteins
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Sulfonamides
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Protein Tyrosine Phosphatases
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yopH protein, Yersinia