7JVU

Crystal structure of human histone deacetylase 8 (HDAC8) I45T mutation complexed with SAHA

7JVU の概要

• エントリーDOI: 10.2210/pdb7jvu/pdb
• 分子名称: Histone deacetylase 8, ZINC ION, POTASSIUM ION, ... (6 entities in total)
• 機能のキーワード: histone deacetylase, hydrolase, cornelia de lange syndrome (cdls)
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 87690.20

構造登録者

Osko, J.D.,Christianson, D.W.,Decroos, C.,Porter, N.J.,Lee, M. (登録日: 2020-08-24, 公開日: 2020-12-16, 最終更新日: 2023-10-18)

主引用文献

Osko, J.D.,Porter, N.J.,Decroos, C.,Lee, M.S.,Watson, P.R.,Raible, S.E.,Krantz, I.D.,Deardorff, M.A.,Christianson, D.W.
Structural analysis of histone deacetylase 8 mutants associated with Cornelia de Lange Syndrome spectrum disorders.
J.Struct.Biol., 213:107681-107681, 2020

PubMed Abstract: Cornelia de Lange Syndrome (CdLS) and associated spectrum disorders are characterized by one or more congenital anomalies including distinctive facial features, upper limb abnormalities, intellectual disability, and other symptoms. The molecular genetic basis of CdLS is linked to defects in cohesin, a protein complex that functions in sister chromatid cohesion, chromatin organization, and transcriptional regulation. Histone deacetylase 8 (HDAC8) plays an important role in cohesin function by catalyzing the deacetylation of SMC3, which is required for efficient recycling of the cohesin complex. Missense mutations in HDAC8 have been identified in children diagnosed with CdLS spectrum disorders, and here we outline structure-function relationships for four of these mutations. Specifically, we report the 1.50 Å-resolution structure of the I45T HDAC8-suberoylanilide hydroxamic acid complex, the 1.84 Å-resolution structure of E66D/Y306F HDAC8 complexed with a peptide assay substrate, and the 2.40 Å-resolution structure of G320R HDAC8 complexed with the inhibitor M344. Additionally, we present a computationally generated model of D176G HDAC8. These structures illuminate new structure-function relationships for HDAC8 and highlight the importance of long-range interactions in the protein scaffold that can influence catalytic function.

PubMed: 33316326
DOI: 10.1016/j.jsb.2020.107681

実験手法

X-RAY DIFFRACTION (1.5004765401 Å)