6OIQ

Crystal structure of MYST acetyltransferase domain in complex with inhibitor 63

6OIQ の概要

• エントリーDOI: 10.2210/pdb6oiq/pdb
• 分子名称: Histone acetyltransferase KAT8, ZINC ION, 2-fluoro-N'-(phenylsulfonyl)[1,1'-biphenyl]-3-carbohydrazide, ... (5 entities in total)
• 機能のキーワード: inhibitor, complex, myst, transferase, transferase-transferase inhibitor complex, transferase/transferase 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: 32667.96

構造登録者

Hermans, S.J.,Chung, M.C.,Parker, M.W.,Thomas, T.,Baell, J.B. (登録日: 2019-04-09, 公開日: 2019-07-03, 最終更新日: 2024-10-23)

主引用文献

Leaver, D.J.,Cleary, B.,Nguyen, N.,Priebbenow, D.L.,Lagiakos, H.R.,Sanchez, J.,Xue, L.,Huang, F.,Sun, Y.,Mujumdar, P.,Mudududdla, R.,Varghese, S.,Teguh, S.,Charman, S.A.,White, K.L.,Katneni, K.,Cuellar, M.,Strasser, J.M.,Dahlin, J.L.,Walters, M.A.,Street, I.P.,Monahan, B.J.,Jarman, K.E.,Sabroux, H.J.,Falk, H.,Chung, M.C.,Hermans, S.J.,Parker, M.W.,Thomas, T.,Baell, J.B.
Discovery of Benzoylsulfonohydrazides as Potent Inhibitors of the Histone Acetyltransferase KAT6A.
J.Med.Chem., 62:7146-7159, 2019

PubMed Abstract: A high-throughput screen for inhibitors of the histone acetyltransferase, KAT6A, led to identification of an aryl sulfonohydrazide derivative (CTX-0124143) that inhibited KAT6A with an IC of 1.0 μM. Elaboration of the structure-activity relationship and medicinal chemistry optimization led to the discovery of WM-8014 (), a highly potent inhibitor of KAT6A (IC = 0.008 μM). WM-8014 competes with acetyl-CoA (Ac-CoA), and X-ray crystallographic analysis demonstrated binding to the Ac-CoA binding site. Through inhibition of KAT6A activity, WM-8014 induces cellular senescence and represents a unique pharmacological tool.

PubMed: 31256587
DOI: 10.1021/acs.jmedchem.9b00665

実験手法

X-RAY DIFFRACTION (1.75 Å)