5QJ3

CRYSTAL STRUCTURE OF MYELOPEROXIDASE SUBFORM C (MPO) COMPLEX WITH COMPOUND-24 AKA 7-({4-CHLORO-3'-FLUORO-[1,1'- BIPHENYL]-3-YL}METHOXY)-3H-[1,2,3]TRIAZOLO[4,5-B]PYRIDIN- 5-AMINE

5QJ3 の概要

• エントリーDOI: 10.2210/pdb5qj3/pdb
• Group deposition: MPO (G_1002056)
• 分子名称: Myeloperoxidase, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, ... (10 entities in total)
• 機能のキーワード: myeloperoxidase, metal binding protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 135686.33

構造登録者

Khan, J.A. (登録日: 2018-09-26, 公開日: 2019-02-06, 最終更新日: 2026-02-18)

主引用文献

Wurtz, N.R.,Viet, A.,Shaw, S.A.,Dilger, A.,Valente, M.N.,Khan, J.A.,Jusuf, S.,Narayanan, R.,Fernando, G.,Lo, F.,Liu, X.,Locke, G.A.,Kopcho, L.,Abell, L.M.,Sleph, P.,Basso, M.,Zhao, L.,Wexler, R.R.,Duclos, F.,Kick, E.K.
Potent Triazolopyridine Myeloperoxidase Inhibitors.
ACS Med Chem Lett, 9:1175-1180, 2018

PubMed Abstract: Myeloperoxidase (MPO) generates reactive oxygen species that potentially contribute to many chronic inflammatory diseases. A recently reported triazolopyrimidine MPO inhibitor was optimized to improve acid stability and remove methyl guanine methyl transferase (MGMT) activity. Multiple synthetic routes were explored that allowed rapid optimization of a key benzyl ether side chain. Crystal structures of inhibitors bound to the MPO active site demonstrated alternate binding modes and guided rational design of MPO inhibitors. Thioether showed significant inhibition of MPO activity in an acute mouse inflammation model after oral dosing.

PubMed: 30613322
DOI: 10.1021/acsmedchemlett.8b00308

実験手法

X-RAY DIFFRACTION (2.76 Å)