1RSI
DHNA complex with 2-Amino-5-bromo-3-hydroxy-6-phenylpyrimidine
Summary for 1RSI
| Entry DOI | 10.2210/pdb1rsi/pdb |
| Related | 1RR5 1RRI 1RRW 1RRY 1RS2 1RS4 1RSD |
| Descriptor | Dihydroneopterin aldolase, 2-AMINO-5-BROMO-6-PHENYLPYRIMIDIN-4-OL (2 entities in total) |
| Functional Keywords | dhna, 7, 8-dihydroneopterin aldolase, 2-amino-5-bromo-3-hydroxy-6-phenylpyrimidine, lyase |
| Biological source | Staphylococcus aureus |
| Total number of polymer chains | 1 |
| Total formula weight | 14035.73 |
| Authors | 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. (deposition date: 2003-12-09, release date: 2004-03-30, Last modification date: 2024-02-14) |
| Primary citation | 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 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.2 Å) |
Structure validation
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