Loop interactions and dynamics tune the enzymatic activity of the human histone deacetylase 8.

ABSTRACT: The human histone deacetylase 8 (HDAC8) is a key hydrolase in gene regulation and has been identified as a drug target for the treatment of several cancers. Previously the HDAC8 enzyme has been extensively studied using biochemical techniques, X-ray crystallography, and computational methods. Those investigations have yielded detailed information about the active site and have demonstrated that the substrate entrance surface is highly dynamic. Yet it has remained unclear how the dynamics of the entrance surface tune and influence the catalytic activity of HDAC8. Using long time scale all atom molecular dynamics simulations we have found a mechanism whereby the interactions and dynamics of two loops tune the configuration of functionally important residues of HDAC8 and could therefore influ

SUBMITTER: Kunze MB 

PROVIDER: S-EPMC3926704 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature