1RRI

DHNA complex with 3-(5-amino-7-hydroxy-[1,2,3] triazolo [4,5-d]pyrimidin-2-yl)-benzoic acid

1RRI の概要

• エントリーDOI: 10.2210/pdb1rri/pdb
• 関連するPDBエントリー: 1RR5 1RRW 1RRY 1RS2 1RS4 1RSD 1RSI
• 分子名称: Dihydroneopterin aldolase, 3-(5-AMINO-7-HYDROXY-[1,2,3]TRIAZOLO[4,5-D]PYRIMIDIN-2-YL)-BENZOIC ACID (2 entities in total)
• 機能のキーワード: dhna complex with 3-(5-amino-7-hydroxy-[1, 2, 3] triazolo [4, 5-d]pyrimidin-2-yl)-benzoic acid, lyase
• 由来する生物種: Staphylococcus aureus
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 14041.85

構造登録者

Sanders, W.J.,Nienaber, V.L.,Lerner, C.G.,McCall, J.O.,Merrick, S.M.,Swanson, S.J.,Harlan, J.E.,Stoll, V.S.,Stamper, G.F.,Betz, S.F.,Condroski, K.R.,Meadows, R.P.,Severin, J.M.,Walter, K.A.,Magdalinos, P.,Jakob, C.G.,Wagner, R.,Beutel, B.A. (登録日: 2003-12-08, 公開日: 2004-03-30, 最終更新日: 2024-02-14)

主引用文献

Sanders, W.J.,Nienaber, V.L.,Lerner, C.G.,McCall, J.O.,Merrick, S.M.,Swanson, S.J.,Harlan, J.E.,Stoll, V.S.,Stamper, G.F.,Betz, S.F.,Condroski, K.R.,Meadows, R.P.,Severin, J.M.,Walter, K.A.,Magdalinos, P.,Jakob, C.G.,Wagner, R.,Beutel, B.A.
Discovery of Potent Inhibitors of Dihydroneopterin Aldolase Using CrystaLEAD High-Throughput X-ray Crystallographic Screening and Structure-Directed Lead Optimization.
J.Med.Chem., 47:1709-1718, 2004

PubMed Abstract: Potent inhibitors of 7,8-dihydroneopterin aldolase (DHNA; EC 4.1.2.25) have been discovered using CrystaLEAD X-ray crystallographic high-throughput screening followed by structure-directed optimization. Screening of a 10 000 compound random library provided several low affinity leads and their corresponding X-ray crystal structures bound to the enzyme. The presence of a common structural feature in each of the leads suggested a strategy for the construction of a directed library of approximately 1000 compounds that were screened for inhibitory activity in a traditional enzyme assay. Several lead compounds with IC(50) values of about 1 microM against DHNA were identified, and crystal structures of their enzyme-bound complexes were obtained by cocrystallization. Structure-directed optimization of one of the leads thus identified afforded potent inhibitors with submicromolar IC(50) values.

PubMed: 15027862
DOI: 10.1021/jm030497y

実験手法

X-RAY DIFFRACTION (2 Å)