Isothiazolidinone (IZD) as a phosphoryl mimetic in inhibitors of the Yersinia pestis protein tyrosine phosphatase YopH.
Acta Crystallogr D Biol Crystallogr
; 67(Pt 7): 639-45, 2011 Jul.
Article
em En
| MEDLINE
| ID: mdl-21697602
ABSTRACT
Isothiazolidinone (IZD) heterocycles can act as effective components of protein tyrosine phosphatase (PTP) inhibitors by simultaneously replicating the binding interactions of both a phosphoryl group and a highly conserved water molecule, as exemplified by the structures of several PTP1B-inhibitor complexes. In the first unambiguous demonstration of IZD interactions with a PTP other than PTP1B, it is shown by X-ray crystallography that the IZD motif binds within the catalytic site of the Yersinia pestis PTP YopH by similarly displacing a highly conserved water molecule. It is also shown that IZD-based bidentate ligands can inhibit YopH in a nonpromiscuous fashion at low micromolar concentrations. Hence, the IZD moiety may represent a useful starting point for the development of YopH inhibitors.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tiazóis
/
Proteínas da Membrana Bacteriana Externa
/
Yersinia pestis
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Proteínas Tirosina Fosfatases
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Materiais Biomiméticos
/
Inibidores de Proteínas Quinases
Idioma:
En
Revista:
Acta Crystallogr D Biol Crystallogr
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos