Conformational response to ligand binding in phosphomannomutase2: insights into inborn glycosylation disorder.

ABSTRACT: The most common glycosylation disorder is caused by mutations in the gene encoding phosphomannomutase2, producing a disease still without a cure. Phosphomannomutase2, a homodimer in which each chain is composed of two domains, requires a bisphosphate sugar (either mannose or glucose) as activator, opening a possible drug design path for therapeutic purposes. The crystal structure of human phosphomannomutase2, however, lacks bound substrate and a key active site loop. To speed up drug discovery, we present here the first structural model of a bisphosphate substrate bound to human phosphomannomutase2. Taking advantage of recent developments in all-atom simulation techniques in combination with limited and site-directed proteolysis, we demonstrated that α-glucose 1,6-bisphosphate can adopt tw

SUBMITTER: Andreotti G 

PROVIDER: S-EPMC4263888 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature