1VKG

Crystal Structure of Human HDAC8 complexed with CRA-19156

Summary for 1VKG

• Entry DOI: 10.2210/pdb1vkg/pdb
• Related: 1T64 1T67 1T69
• Descriptor: Histone deacetylase 8, ZINC ION, SODIUM ION, ... (5 entities in total)
• Functional Keywords: histone deacetylase, zinc hydrolase, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: Q9BY41
• Total number of polymer chains: 2
• Total formula weight: 84616.67

Authors

Somoza, J.R.,Skene, R.J.,Katz, B.A.,Mol, C.,Ho, J.D.,Jennings, A.J.,Luong, C.,Arvai, A.,Buggy, J.J.,Chi, E.,Tang, J.,Sang, B.-C.,Verner, E.,Wynands, R.,Leahy, E.M.,Dougan, D.R.,Snell, G.,Navre, M.,Knuth, M.W.,Swanson, R.V.,McRee, D.E.,Tari, L.W. (deposition date: 2004-05-13, release date: 2004-07-27, Last modification date: 2024-11-13)

Primary citation

Somoza, J.R.,Skene, R.J.,Katz, B.A.,Mol, C.,Ho, J.D.,Jennings, A.J.,Luong, C.,Arvai, A.,Buggy, J.J.,Chi, E.,Tang, J.,Sang, B.-C.,Verner, E.,Wynands, R.,Leahy, E.M.,Dougan, D.R.,Snell, G.,Navre, M.,Knuth, M.W.,Swanson, R.V.,McRee, D.E.,Tari, L.W.
Structural Snapshots of Human HDAC8 Provide Insights into the Class I Histone Deacetylases
Structure, 12:1325-1334, 2004

PubMed Abstract: Modulation of the acetylation state of histones plays a pivotal role in the regulation of gene expression. Histone deacetylases (HDACs) catalyze the removal of acetyl groups from lysines near the N termini of histones. This reaction promotes the condensation of chromatin, leading to repression of transcription. HDAC deregulation has been linked to several types of cancer, suggesting a potential use for HDAC inhibitors in oncology. Here we describe the first crystal structures of a human HDAC: the structures of human HDAC8 complexed with four structurally diverse hydroxamate inhibitors. This work sheds light on the catalytic mechanism of the HDACs, and on differences in substrate specificity across the HDAC family. The structure also suggests how phosphorylation of Ser39 affects HDAC8 activity.

PubMed: 15242608
DOI: 10.1016/j.str.2004.04.012

Experimental method

X-RAY DIFFRACTION (2.2 Å)