Ontology highlight
ABSTRACT:
SUBMITTER: Wu R
PROVIDER: S-EPMC3086135 | biostudies-literature | 2011 Apr
REPOSITORIES: biostudies-literature
Wu Ruibo R Lu Zhenyu Z Cao Zexing Z Zhang Yingkai Y
Journal of the American Chemical Society 20110401 16
It is of significant biological interest and medical importance to develop class- and isoform-selective histone deacetylase (HDAC) modulators. The impact of the linker component on HDAC inhibition specificity has been revealed but is not understood. Using Born-Oppenheimer ab initio QM/MM MD simulations, a state-of-the-art approach to simulating metallo-enzymes, we have found that the hydroxamic acid remains to be protonated upon its binding to HDAC8, and thus disproved the mechanistic hypothesis ...[more]