Targeting Nonconserved and Pathogenic Cysteines of Protein Tyrosine Phosphatases with Small Molecules.
Methods Mol Biol
; 2743: 271-283, 2024.
Article
em En
| MEDLINE
| ID: mdl-38147221
ABSTRACT
Protein tyrosine phosphatases (PTPs) are important therapeutic targets for a range of human pathologies. However, the common architecture of PTP active sites impedes the discovery of selective PTP inhibitors. Our laboratory has recently developed methods to inhibit PTPs allosterically by targeting cysteine residues that either (i) are not conserved in the PTP family or (ii) result from pathogenic mutations. Here, we describe screening protocols for the identification of selective inhibitors that covalently engage such "rare" cysteines in target PTPs. Moreover, to elucidate the breadth of possible applications of our cysteine-directed screening protocols, we provide a brief overview of the nonconserved cysteines present in all human classical PTP domains.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Proteínas Tirosina Fosfatases
/
Cisteína
Limite:
Humans
Idioma:
En
Revista:
Methods Mol Biol
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos