1rrw
From Proteopedia
(New page: 200px<br /><applet load="1rrw" size="450" color="white" frame="true" align="right" spinBox="true" caption="1rrw, resolution 2.21Å" /> '''DHNA complexed with ...) |
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| - | [[Image:1rrw.gif|left|200px]]<br /><applet load="1rrw" size=" | + | [[Image:1rrw.gif|left|200px]]<br /><applet load="1rrw" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1rrw, resolution 2.21Å" /> | caption="1rrw, resolution 2.21Å" /> | ||
'''DHNA complexed with 9-methylguanine'''<br /> | '''DHNA complexed with 9-methylguanine'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Potent inhibitors of 7,8-dihydroneopterin aldolase (DHNA; EC 4.1.2.25) | + | 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. |
==About this Structure== | ==About this Structure== | ||
| - | 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 9MG 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:// | + | 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]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Staphylococcus aureus]] | [[Category: Staphylococcus aureus]] | ||
| - | [[Category: Betz, S | + | [[Category: Betz, S F.]] |
| - | [[Category: Beutel, B | + | [[Category: Beutel, B A.]] |
| - | [[Category: Condroski, K | + | [[Category: Condroski, K R.]] |
| - | [[Category: Harlan, J | + | [[Category: Harlan, J E.]] |
| - | [[Category: Jakob, C | + | [[Category: Jakob, C G.]] |
| - | [[Category: Lerner, C | + | [[Category: Lerner, C G.]] |
[[Category: Magdalinos, P.]] | [[Category: Magdalinos, P.]] | ||
| - | [[Category: McCall, J | + | [[Category: McCall, J O.]] |
| - | [[Category: Meadows, R | + | [[Category: Meadows, R P.]] |
| - | [[Category: Merrick, S | + | [[Category: Merrick, S M.]] |
| - | [[Category: Nienaber, V | + | [[Category: Nienaber, V L.]] |
| - | [[Category: Sanders, W | + | [[Category: Sanders, W J.]] |
| - | [[Category: Severin, J | + | [[Category: Severin, J M.]] |
| - | [[Category: Stamper, G | + | [[Category: Stamper, G F.]] |
| - | [[Category: Stoll, V | + | [[Category: Stoll, V S.]] |
| - | [[Category: Swanson, S | + | [[Category: Swanson, S J.]] |
[[Category: Wagner, R.]] | [[Category: Wagner, R.]] | ||
| - | [[Category: Walter, K | + | [[Category: Walter, K A.]] |
[[Category: 9MG]] | [[Category: 9MG]] | ||
[[Category: dhna complexed with 9-methylguanine]] | [[Category: dhna complexed with 9-methylguanine]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:53:57 2008'' |
Revision as of 12:54, 21 February 2008
|
DHNA complexed with 9-methylguanine
Overview
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.
About this Structure
1RRW is a Single protein structure of sequence from Staphylococcus aureus with as ligand. Active as Dihydroneopterin aldolase, with EC number 4.1.2.25 Full crystallographic information is available from OCA.
Reference
Discovery of potent inhibitors of dihydroneopterin aldolase using CrystaLEAD high-throughput X-ray crystallographic screening and structure-directed lead optimization., Sanders WJ, Nienaber VL, Lerner CG, McCall JO, Merrick SM, Swanson SJ, Harlan JE, Stoll VS, Stamper GF, Betz SF, Condroski KR, Meadows RP, Severin JM, Walter KA, Magdalinos P, Jakob CG, Wagner R, Beutel BA, J Med Chem. 2004 Mar 25;47(7):1709-18. PMID:15027862
Page seeded by OCA on Thu Feb 21 14:53:57 2008
Categories: Dihydroneopterin aldolase | Single protein | Staphylococcus aureus | Betz, S F. | Beutel, B A. | Condroski, K R. | Harlan, J E. | Jakob, C G. | Lerner, C G. | Magdalinos, P. | McCall, J O. | Meadows, R P. | Merrick, S M. | Nienaber, V L. | Sanders, W J. | Severin, J M. | Stamper, G F. | Stoll, V S. | Swanson, S J. | Wagner, R. | Walter, K A. | 9MG | Dhna complexed with 9-methylguanine
