in complex with inhibitors tolrestat, 2-(carboxymethyl)-1-oxo-1,2-dihydronaphtho[1,2-d]isothiazole-4-carboxylic acid 3,3-dioxide and 2-[2-(carboxymethoxy)-2-oxoethyl]-1-oxo-1,2-dihydronaphtho[1,2-d]isothiazole-4-carboxylic acid 3,3-dioxide. Unlike tolrestat, the naphthol[1,2-d]isothiazole inhibitors leave the specificity pocket in the closed state and ligand 2-(carboxymethyl)-1-oxo-1,2-dihydronaphtho[1,2-d]isothiazole-4-carboxylic acid 3,3-dioxide extends the catalytic pocket by opening a novel subpocket. Inhibitor 2-[2-(carboxymethoxy)-2-oxoethyl]-1-oxo-1,2-dihydronaphtho[1,2-d]isothiazole-4-carboxylic acid 3,3-dioxide provokes less pronounced induced-fit adaptations of the binding cavity |
Homo sapiens |