3C0Y

Crystal structure of catalytic domain of human histone deacetylase HDAC7

Replaces:  2NVRReplaces:  2I4Y

Summary for 3C0Y

• Entry DOI: 10.2210/pdb3c0y/pdb
• Related: 2NVR 3C0Z 3C10
• Descriptor: Histone deacetylase 7a, ZINC ION, POTASSIUM ION, ... (4 entities in total)
• Functional Keywords: histone deacetylase, structural genomics, structural genomics consortium, sgc, alternative splicing, chromatin regulator, cytoplasm, hydrolase, nucleus, phosphoprotein, polymorphism, repressor, transcription, transcription regulation
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: Q8WUI4
• Total number of polymer chains: 3
• Total formula weight: 137182.06

Authors

Min, J.R.,Schuetz, A.,Allali-Hassani, A.,Loppnau, P.,Kwiatkowski, N.P.,Mazitschek, R.,Weigelt, J.,Sundstrom, M.,Arrowsmith, C.H.,Edwards, A.M.,Vedadi, M.,Bochkarev, A.,Plotnikov, A.N.,Structural Genomics Consortium (SGC) (deposition date: 2008-01-21, release date: 2008-02-19, Last modification date: 2023-08-30)

Primary citation

Schuetz, A.,Min, J.,Allali-Hassani, A.,Schapira, M.,Shuen, M.,Loppnau, P.,Mazitschek, R.,Kwiatkowski, N.P.,Lewis, T.A.,Maglathin, R.L.,McLean, T.H.,Bochkarev, A.,Plotnikov, A.N.,Vedadi, M.,Arrowsmith, C.H.
Human HDAC7 harbors a class IIa histone deacetylase-specific zinc binding motif and cryptic deacetylase activity.
J.Biol.Chem., 283:11355-11363, 2008

PubMed Abstract: 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.

PubMed: 18285338
DOI: 10.1074/jbc.M707362200

Experimental method

X-RAY DIFFRACTION (2.1 Å)