5EFN
Crystal structure of Danio rerio histone deacetylase 6 catalytic domain 2 (H574A) in complex with histone H4 Lys6 tripeptide substrate
Summary for 5EFN
| Entry DOI | 10.2210/pdb5efn/pdb |
| Related | 5EDU 5EEF 5EEI 5EEK 5EEM 5EEN 5EF7 5EF8 5EFB 5EFG 5EFH 5EFJ 5EFK |
| Descriptor | Hdac6 protein, histone H4 tripeptide, ZINC ION, ... (7 entities in total) |
| Functional Keywords | hydrolase |
| Biological source | Danio rerio (Zebrafish) More |
| Total number of polymer chains | 4 |
| Total formula weight | 82101.59 |
| Authors | Hai, Y.,Christianson, D.W. (deposition date: 2015-10-24, release date: 2016-07-27, Last modification date: 2023-11-15) |
| Primary citation | Hai, Y.,Christianson, D.W. Histone deacetylase 6 structure and molecular basis of catalysis and inhibition. Nat.Chem.Biol., 12:741-747, 2016 Cited by PubMed Abstract: Histone deacetylase 6 (HDAC6) is a critical target for drug design because of its role in oncogenic transformation and cancer metastasis, and is unique among all histone deacetylases in that it contains tandem catalytic domains designated CD1 and CD2. We now report the crystal structures of CD2 from Homo sapiens HDAC6 and of CD1 and CD2 from Danio rerio HDAC6. We correlated these structures with activity measurements using 13 different substrates. The catalytic activity of CD2 from both species exhibited broad substrate specificity, whereas that of CD1 was highly specific for substrates bearing C-terminal acetyllysine residues. Crystal structures of substrate complexes yielded unprecedented snapshots of the catalytic mechanism. Additionally, crystal structures of complexes with eight different inhibitors, including belinostat and panobinostat (currently used in cancer chemotherapy), the macrocyclic tetrapeptide HC toxin, and the HDAC6-specific inhibitor N-hydroxy-4-(2-((2-hydroxyethyl)(phenyl)amino)-2-oxoethyl)benzamide, revealed surprising new insight regarding changes in Zn(2+) coordination and isozyme-specific inhibition. PubMed: 27454933DOI: 10.1038/nchembio.2134 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.804 Å) |
Structure validation
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