Anno2016
AutoriBruno S, Margiotta M, Pinto A, Cullia G, Conti P, De Micheli C, Mozzarelli A
AbstractCompounds based on the 3-Br-isoxazoline scaffold fully inhibit glyceraldehyde 3-phosphate dehydrogenase from Plasmodium falciparum by selectively alkylating all four catalytic cysteines of the tetramer. Here, we show that, under the same experimental conditions that led to a fast and complete inhibition of the protozoan enzyme, the human ortholog was only 25% inhibited, with the alkylation of a single catalytic cysteine within the tetramer. The partial alkylation seems to produce a slow conformational rearrangement that severely limits the accessibility of the remaining active sites to bulky 3-Br-isoxazoline derivatives, but not to the substrate or smaller alkylating agents.
RivistaBioorganic & Medicinal Chemistry (print)
ISSN0968-0896
Impact factor
Volume24
Pagina inizio2654
Pagina fine2659
Autori IBFAndrea MOZZARELLI
Linee di Ricerca IBFMD.P01.008.001
Sedi IBFIBF.PI