1rrw: Difference between revisions

[[Image:1rrw.gif|left|200px]]<br /><applet load="1rrw" size="350" color="white" frame="true" align="right" spinBox="true"  

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.

1RRW is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus] with <scene name='pdbligand=9MG:'>9MG</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Dihydroneopterin_aldolase Dihydroneopterin aldolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.2.25 4.1.2.25] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RRW OCA].  

[[Category: Betz, S F.]]

[[Category: Beutel, B A.]]

[[Category: Condroski, K R.]]

[[Category: Harlan, J E.]]

[[Category: Jakob, C G.]]

[[Category: Lerner, C G.]]

[[Category: McCall, J O.]]

[[Category: Meadows, R P.]]

[[Category: Merrick, S M.]]

[[Category: Nienaber, V L.]]

[[Category: Sanders, W J.]]

[[Category: Severin, J M.]]

[[Category: Stamper, G F.]]

[[Category: Stoll, V S.]]

[[Category: Swanson, S J.]]

[[Category: Walter, K A.]]

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:53:57 2008''