Ontology highlight
ABSTRACT:
SUBMITTER: Gertz M
PROVIDER: S-EPMC3725051 | biostudies-literature | 2013 Jul
REPOSITORIES: biostudies-literature
Gertz Melanie M Fischer Frank F Nguyen Giang Thi Tuyet GT Lakshminarasimhan Mahadevan M Schutkowski Mike M Weyand Michael M Steegborn Clemens C
Proceedings of the National Academy of Sciences of the United States of America 20130709 30
Sirtuins are protein deacetylases regulating metabolism and stress responses. The seven human Sirtuins (Sirt1-7) are attractive drug targets, but Sirtuin inhibition mechanisms are mostly unidentified. We report the molecular mechanism of Sirtuin inhibition by 6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide (Ex-527). Inhibitor binding to potently inhibited Sirt1 and Thermotoga maritima Sir2 and to moderately inhibited Sirt3 requires NAD(+), alone or together with acetylpeptide. Crystal str ...[more]