3VW9

Human Glyoxalase I with an N-hydroxypyridone inhibitor

3VW9 の概要

• エントリーDOI: 10.2210/pdb3vw9/pdb
• 分子名称: Lactoylglutathione lyase, ZINC ION, 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID, ... (5 entities in total)
• 機能のキーワード: glyoxalase, lyase-lyase inhibitor complex, lyase/lyase inhibitor
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 43291.94

構造登録者

Fukami, T.A.,Irie, M.,Matsuura, T. (登録日: 2012-08-10, 公開日: 2012-12-12, 最終更新日: 2023-11-08)

主引用文献

Chiba, T.,Ohwada, J.,Sakamoto, H.,Kobayashi, T.,Fukami, T.A.,Irie, M.,Miura, T.,Ohara, K.,Koyano, H.
Design and evaluation of azaindole-substituted N-hydroxypyridones as glyoxalase I inhibitors
Bioorg.Med.Chem.Lett., 22:7486-7489, 2012

PubMed Abstract: We conducted a high throughput screening for glyoxalase I (GLO1) inhibitors and identified 4,6-diphenyl-N-hydroxypyridone as a lead compound. Using a binding model of the lead and public X-ray coordinates of GLO1 enzymes complexed with glutathione analogues, we designed 4-(7-azaindole)-substituted 6-phenyl-N-hydroxypyridones. 7-Azaindole's 7-nitrogen was expected to interact with a water network, resulting in an interaction with the protein. We validated this inhibitor design by comparing its structure-activity relationship (SAR) with that of corresponding indole derivatives, by analyzing the binding mode with X-ray crystallography and by evaluating its thermodynamic binding parameters.

PubMed: 23122816
DOI: 10.1016/j.bmcl.2012.10.045

実験手法

X-RAY DIFFRACTION (1.47 Å)