1U68 の概要
エントリーDOI | 10.2210/pdb1u68/pdb |
分子名称 | Dihydroneopterin aldolase, 2-AMINO-7,8-DIHYDRO-6-(1,2,3-TRIHYDROXYPROPYL)-4(1H)-PTERIDINONE (2 entities in total) |
機能のキーワード | dhna, 7, 8 dihydroneopterin, 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 | 14024.87 |
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: 2004-07-29, 公開日: 2004-10-19, 最終更新日: 2024-12-25) |
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 Cited by 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: 15027862DOI: 10.1021/jm030497y 主引用文献が同じPDBエントリー |
実験手法 | X-RAY DIFFRACTION (2.4 Å) |
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