Summary
PDB 3C10 deposited: 2008-01-21 modified: 2009-10-27
Title Crystal structure of catalytic domain of human histone deacetylase HDAC7 in complex with Trichostatin A (TSA)
Authors Allali-Hassani, A., Arrowsmith, C.H., Bochkarev, A., Kwiatkowski, N.P., Lewis, T.A., Loppnau, P., Maglathin, R.L., Mazitschek, R., McLean, T.H., Min, J., Plotnikov, A.N., Schapira, M., Schuetz, A., Shuen, M., Vedadi, M.
Method X-RAY DIFFRACTION
Structure factors resolution 2.0 rfactor 0.20126 rfree 0.26312
DPI 0.50 theoretical min: 0.21
Related PDB Entries 3C0Y 3C0Z
Citations

Histone deacetylases (HDACs) are protein deacetylases that play a role in repression of gene transcription and are emerging targets in cancer therapy. Here, we characterize the structure and enzymatic activity of the catalytic domain of human HDAC7 (cdHDAC7). Although HDAC7 normally exists as part of a multiprotein complex, we show that cdHDAC7 has a low level of deacetylase activity which can be inhibited by known HDAC inhibitors. The crystal structures of human cdHDAC7 and its complexes with two hydroxamate inhibitors are the first structures of the catalytic domain of class IIa HDACs and demonstrate significant differences with previously reported class I and class IIb-like HDAC structures. We show that cdHDAC7 has an additional class IIa HDAC-specific zinc binding motif adjacent to the active site which is likely to participate in substrate recognition and protein-protein interaction and may provide a site for modulation of activity. Furthermore, a different active site topology results in modified catalytic properties and in an enlarged active site pocket. Our studies provide mechanistic insights into class IIa HDACs and facilitate the design of specific modulators.

J.Biol.Chem. 2008 Apr; 283(17):11355-11363 doi:10.1074/jbc.M707362200

Cross References
Database source Identifier Description
PubMed 18285338 JBCHA3
Biomolecule Structure Assembly Serial Assembly Type Conformational State Chains Ligands Atoms
3C10/1 3C10 1 monomer 0 1 5 2464
3C10/2 3C10 2 monomer 0 1 5 2328
3C10/3 3C10 3 monomer 0 1 5 2247