6PZU

Crystal structure of Danio rerio histone deacetylase 6 catalytic domain 2 complexed with AP-1-62-A

6PZU の概要

• エントリーDOI: 10.2210/pdb6pzu/pdb
• 分子名称: Hdac6 protein, ZINC ION, POTASSIUM ION, ... (5 entities in total)
• 機能のキーワード: histone deacetylase, metallohydrolase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Danio rerio (Zebrafish)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 80706.25

構造登録者

Osko, J.D.,Christianson, D.W. (登録日: 2019-08-01, 公開日: 2020-02-05, 最終更新日: 2023-10-11)

主引用文献

Osko, J.D.,Porter, N.J.,Narayana Reddy, P.A.,Xiao, Y.C.,Rokka, J.,Jung, M.,Hooker, J.M.,Salvino, J.M.,Christianson, D.W.
Exploring Structural Determinants of Inhibitor Affinity and Selectivity in Complexes with Histone Deacetylase 6.
J.Med.Chem., 63:295-308, 2020

PubMed Abstract: Inhibition of histone deacetylase 6 (HDAC6) has emerged as a promising therapeutic strategy for the treatment of cancer, chemotherapy-induced peripheral neuropathy, and neurodegenerative disease. The recent X-ray crystal structure determination of HDAC6 enables an understanding of structural features directing affinity and selectivity in the active site. Here, we present the X-ray crystal structures of five HDAC6-inhibitor complexes that illuminate key molecular features of the inhibitor linker and capping groups that facilitate and differentiate binding to HDAC6. In particular, aromatic and heteroaromatic linkers nestle within an aromatic cleft defined by F583 and F643, and different aromatic linkers direct the capping group toward shallow pockets defined by the L1 loop, the L2 loop, or somewhere in between these pockets. These results expand our understanding of factors contributing to the selective inhibition of HDAC6, particularly regarding interactions that can be targeted in the region of the L2 pocket.

PubMed: 31793776
DOI: 10.1021/acs.jmedchem.9b01540

実験手法

X-RAY DIFFRACTION (1.74 Å)