title: Synthetic chalcones and sulfonamides as new classes of Yersinia enterocolitica YopH tyrosine phosphatase inhibitors.
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.
authors: Centro de Biologia Molecular Estrutural (CEBIME), Departamento de Bioquímica, Universidade Federal de Santa Catarina, Campus Trindade, 88040-900 Florianópolis, SC, Brazil.
authors: Priscila Graziela Alves
authors: PG
authors: Martins
authors: Angela Camila Orbem
authors: AC
authors: Menegatti
authors: Louise Domeneghini
authors: LD
authors: Chiaradia-Delatorre
authors: Kely Navakoski
authors: KN
authors: de Oliveira
authors: Rafael Victorio Carvalho
authors: RV
authors: Guido
authors: Adriano Defini
authors: AD
authors: Andricopulo
authors: Javier
authors: J
authors: Vernal
authors: Rosendo Augusto
authors: RA
authors: Yunes
authors: Ricardo José
authors: RJ
authors: Nunes
authors: Hernán
authors: H
authors: Terenzi
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000037:antagonists & inhibitors* / Q000302:isolation & purification / Q000378:metabolism; D047188:Chalcones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D007700:Kinetics; D008958:Models, Molecular; D015394:Molecular Structure; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors* / Q000302:isolation & purification / Q000378:metabolism; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000378:metabolism; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015008:Yersinia enterocolitica / Q000201:enzymology*
chemical_list: D001425:Bacterial Outer Membrane Proteins; D047188:Chalcones; D004791:Enzyme Inhibitors; D011994:Recombinant Proteins; D013449:Sulfonamides; D017027:Protein Tyrosine Phosphatases; C067571:yopH protein, Yersinia