1rs2: Difference between revisions
New page: left|200px<br /><applet load="1rs2" size="450" color="white" frame="true" align="right" spinBox="true" caption="1rs2, resolution 2.31Å" /> '''DHNA complex with 8-... |
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[[Image:1rs2.gif|left|200px]]<br /><applet load="1rs2" size=" | [[Image:1rs2.gif|left|200px]]<br /><applet load="1rs2" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1rs2, resolution 2.31Å" /> | caption="1rs2, resolution 2.31Å" /> | ||
'''DHNA complex with 8-Amino-1,3-dimethyl-3,7-dihydropurine-2,6-dione'''<br /> | '''DHNA complex with 8-Amino-1,3-dimethyl-3,7-dihydropurine-2,6-dione'''<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== | ||
1RS2 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 209 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:// | 1RS2 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=209:'>209</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=1RS2 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: 209]] | [[Category: 209]] | ||
[[Category: 3-dimethyl-3]] | [[Category: 3-dimethyl-3]] | ||
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[[Category: dhna]] | [[Category: dhna]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:54:00 2008'' | ||
Revision as of 15:54, 21 February 2008
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DHNA complex with 8-Amino-1,3-dimethyl-3,7-dihydropurine-2,6-dione
OverviewOverview
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 StructureAbout this Structure
1RS2 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.
ReferenceReference
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 14:54:00 2008
Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)
OCA- Pages with broken file links
- 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.
- 209
- 3-dimethyl-3
- 6-dioneterin aldolase
- 7
- 7-dihydropurine-2
- 8-dihydroneop8-amino-1
- Dhna