5G1C

Structure of HDAC like protein from Bordetella Alcaligenes bound the photoswitchable pyrazole Inhibitor CEW395

5G1C の概要

• エントリーDOI: 10.2210/pdb5g1c/pdb
• 関連するPDBエントリー: 5G0X 5G0Y 5G10 5G11 5G12 5G13 5G14 5G17 5G1A 5G1B
• 分子名称: HISTONE DEACETYLASE-LIKE AMIDOHYDROLASE, ZINC ION, POTASSIUM ION, ... (7 entities in total)
• 機能のキーワード: hydrolase, hdah, hdac, hdlp
• 由来する生物種: ALCALIGENES
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 81244.66

構造登録者

Kraemer, A.,Meyer-Almes, F.J.,Yildiz, O. (登録日: 2016-03-24, 公開日: 2016-11-23, 最終更新日: 2024-01-10)

主引用文献

Weston, C.E.,Kramer, A.,Colin, F.,Yildiz, O.,Baud, M.G.,Meyer-Almes, F.J.,Fuchter, M.J.
Toward Photopharmacological Antimicrobial Chemotherapy Using Photoswitchable Amidohydrolase Inhibitors.
ACS Infect Dis, 3:152-161, 2017

PubMed Abstract: Photopharmacological agents exhibit light-dependent biological activity and may have potential in the development of new antimicrobial agents/modalities. Amidohydrolase enzymes homologous to the well-known human histone deacetylases (HDACs) are present in bacteria, including resistant organisms responsible for a significant number of hospital-acquired infections and deaths. We report photopharmacological inhibitors of these enzymes, using two classes of photoswitches embedded in the inhibitor pharmacophore: azobenzenes and arylazopyrazoles. Although both classes of inhibitor show excellent inhibitory activity (nM IC values) of the target enzymes and promising differential activity of the switchable E- and Z-isomeric forms, the arylazopyrazoles exhibit better intrinsic photoswitch performance (more complete switching, longer thermal lifetime of the Z-isomer). We also report protein-ligand crystal structures of the E-isomers of both an azobenzene and an arylazopyrazole inhibitor, bound to bacterial histone deacetylase-like amidohydrolases (HDAHs). These structures not only uncover interactions important for inhibitor binding but also reveal conformational differences between the two photoswitch inhibitor classes. As such, our data may pave the way for the design of improved photopharmacological agents targeting the HDAC superfamily.

PubMed: 27756124
DOI: 10.1021/acsinfecdis.6b00148

実験手法

X-RAY DIFFRACTION (1.81 Å)