Exploring ligand interactions with human phosphomannomutases using recombinant bacterial thermal shift assay and biochemical validation.
Biochimie
; 222: 123-131, 2024 Jul.
Article
em En
| MEDLINE
| ID: mdl-38458414
ABSTRACT
PMM2-CDG, a disease caused by mutations in phosphomannomutase-2, is the most common congenital disorder of glycosylation. Yet, it still lacks a cure. Targeting phosphomannomutase-2 with pharmacological chaperones or inhibiting the phosphatase activity of phosphomannomutase-1 to enhance intracellular glucose-1,6-bisphosphate have been proposed as therapeutical approaches. We used Recombinant Bacterial Thermal Shift Assay to assess the binding of a substrate analog to phosphomannomutase-2 and the specific binding to phosphomannomutase-1 of an FDA-approved drug - clodronate. We also deepened the clodronate binding by enzyme activity assays and in silico docking. Our results confirmed the selective binding of clodronate to phosphomannomutase-1 and shed light on such binding.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fosfotransferases (Fosfomutases)
Limite:
Humans
Idioma:
En
Revista:
Biochimie
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Itália