5WPB

Crystal structure of fragment 3-(3-(pyridin-2-ylmethoxy)quinoxalin-2-yl)propanoic acid bound in the ubiquitin binding pocket of the HDAC6 zinc-finger domain

5WPB の概要

• エントリーDOI: 10.2210/pdb5wpb/pdb
• 分子名称: Histone deacetylase 6, ZINC ION, 3-{3-[(pyridin-2-yl)methoxy]quinoxalin-2-yl}propanoic acid, ... (5 entities in total)
• 機能のキーワード: histone deacetylase, hdac, hdac6, fragment screening, structural genomics consortium, sgc, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 12133.75

構造登録者

Harding, R.J.,Tempel, W.,Ferreira de Freitas, R.,Franzoni, I.,Ravichandran, M.,Lautens, M.,Santhakumar, V.,Schapira, M.,Bountra, C.,Edwards, A.M.,Arrowsmith, C.H.,Structural Genomics Consortium (SGC) (登録日: 2017-08-04, 公開日: 2017-08-23, 最終更新日: 2024-03-13)

主引用文献

Harding, R.J.,Ferreira de Freitas, R.,Collins, P.,Franzoni, I.,Ravichandran, M.,Ouyang, H.,Juarez-Ornelas, K.A.,Lautens, M.,Schapira, M.,von Delft, F.,Santhakumar, V.,Arrowsmith, C.H.
Small Molecule Antagonists of the Interaction between the Histone Deacetylase 6 Zinc-Finger Domain and Ubiquitin.
J. Med. Chem., 60:9090-9096, 2017

PubMed Abstract: Inhibitors of HDAC6 have attractive potential in numerous cancers. HDAC6 inhibitors to date target the catalytic domains, but targeting the unique zinc-finger ubiquitin-binding domain (Zf-UBD) of HDAC6 may be an attractive alternative strategy. We developed X-ray crystallography and biophysical assays to identify and characterize small molecules capable of binding to the Zf-UBD and competing with ubiquitin binding. Our results revealed two adjacent ligand-able pockets of HDAC6 Zf-UBD and the first functional ligands for this domain.

PubMed: 29019676
DOI: 10.1021/acs.jmedchem.7b00933

実験手法

X-RAY DIFFRACTION (1.55 Å)