Schistosome sirtuins as drug targets.
Fiche publication
Date publication
janvier 2015
Journal
Future medicinal chemistry
Auteurs
Membres identifiés du Cancéropôle Est :
Dr ROMIER Christophe
Tous les auteurs :
Lancelot J, Cabezas-Cruz A, Caby S, Marek M, Schultz J, Romier C, Sippl W, Jung M, Pierce RJ
Lien Pubmed
Résumé
The sirtuins form a superfamily of evolutionarily conserved NAD(+)-dependent protein N-ϵ-acyl-lysine (AcK) deacylases with roles in a variety of key cellular processes. Sirtuins have a broadly conserved overall structure with a catalytic site formed by a hydrophobic channel between the NAD(+)-binding Rossmann fold domain and a smaller Zn(2+)-binding domain. Schistosomes express five members of the sirtuin family and generic sirtuin inhibitors induce apoptosis and death in schistosome larvae, the disruption of adult worm pairs, inhibition of egg laying and damage to the male and female worm reproductive systems. Sirtuins in schistosomes and other parasitic flatworms present structural differences from their human orthologues that should allow the development of selective inhibitors that can be developed as drug leads.
Mots clés
Amino Acid Sequence, Animals, Anthelmintics, chemistry, Drug Discovery, methods, Helminth Proteins, antagonists & inhibitors, Humans, Models, Molecular, Molecular Sequence Data, Molecular Targeted Therapy, methods, Schistosoma, chemistry, Schistosomiasis, drug therapy, Sequence Alignment, Sirtuins, antagonists & inhibitors
Référence
Future Med Chem. 2015 ;7(6):765-82