1rs2

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (08:25, 14 February 2024) (edit) (undo)
 
(13 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:1rs2.gif|left|200px]]<br /><applet load="1rs2" size="350" color="white" frame="true" align="right" spinBox="true"
 
-
caption="1rs2, resolution 2.31&Aring;" />
 
-
'''DHNA complex with 8-Amino-1,3-dimethyl-3,7-dihydropurine-2,6-dione'''<br />
 
-
==Overview==
+
==DHNA complex with 8-Amino-1,3-dimethyl-3,7-dihydropurine-2,6-dione==
-
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.
+
<StructureSection load='1rs2' size='340' side='right'caption='[[1rs2]], [[Resolution|resolution]] 2.31&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[1rs2]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RS2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1RS2 FirstGlance]. <br>
 +
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.31&#8491;</td></tr>
 +
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=209:8-AMINO-1,3-DIMETHYL-3,7-DIHYDROPURINE-2,6-DIONE'>209</scene></td></tr>
 +
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1rs2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1rs2 OCA], [https://pdbe.org/1rs2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1rs2 RCSB], [https://www.ebi.ac.uk/pdbsum/1rs2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1rs2 ProSAT]</span></td></tr>
 +
</table>
 +
== Function ==
 +
[https://www.uniprot.org/uniprot/FOLB_STAAU FOLB_STAAU] Catalyzes the conversion of 7,8-dihydroneopterin to 6-hydroxymethyl-7,8-dihydropterin.
 +
== Evolutionary Conservation ==
 +
[[Image:Consurf_key_small.gif|200px|right]]
 +
Check<jmol>
 +
<jmolCheckbox>
 +
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/rs/1rs2_consurf.spt"</scriptWhenChecked>
 +
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
 +
<text>to colour the structure by Evolutionary Conservation</text>
 +
</jmolCheckbox>
 +
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1rs2 ConSurf].
 +
<div style="clear:both"></div>
-
==About this Structure==
+
==See Also==
-
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].
+
*[[Aldolase 3D structures|Aldolase 3D structures]]
-
 
+
*[[Chorismate synthase|Chorismate synthase]]
-
==Reference==
+
__TOC__
-
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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15027862 15027862]
+
</StructureSection>
-
[[Category: Dihydroneopterin aldolase]]
+
[[Category: Large Structures]]
-
[[Category: Single protein]]
+
[[Category: Staphylococcus aureus]]
[[Category: Staphylococcus aureus]]
-
[[Category: Betz, S F.]]
+
[[Category: Betz SF]]
-
[[Category: Beutel, B A.]]
+
[[Category: Beutel BA]]
-
[[Category: Condroski, K R.]]
+
[[Category: Condroski KR]]
-
[[Category: Harlan, J E.]]
+
[[Category: Harlan JE]]
-
[[Category: Jakob, C G.]]
+
[[Category: Jakob CG]]
-
[[Category: Lerner, C G.]]
+
[[Category: Lerner CG]]
-
[[Category: Magdalinos, P.]]
+
[[Category: Magdalinos P]]
-
[[Category: McCall, J O.]]
+
[[Category: McCall JO]]
-
[[Category: Meadows, R P.]]
+
[[Category: Meadows RP]]
-
[[Category: Merrick, S M.]]
+
[[Category: Merrick SM]]
-
[[Category: Nienaber, V L.]]
+
[[Category: Nienaber VL]]
-
[[Category: Sanders, W J.]]
+
[[Category: Sanders WJ]]
-
[[Category: Severin, J M.]]
+
[[Category: Severin JM]]
-
[[Category: Stamper, G F.]]
+
[[Category: Stamper GF]]
-
[[Category: Stoll, V S.]]
+
[[Category: Stoll VS]]
-
[[Category: Swanson, S J.]]
+
[[Category: Swanson SJ]]
-
[[Category: Wagner, R.]]
+
[[Category: Wagner R]]
-
[[Category: Walter, K A.]]
+
[[Category: Walter KA]]
-
[[Category: 209]]
+
-
[[Category: 3-dimethyl-3]]
+
-
[[Category: 6-dioneterin aldolase]]
+
-
[[Category: 7]]
+
-
[[Category: 7-dihydropurine-2]]
+
-
[[Category: 8-dihydroneop8-amino-1]]
+
-
[[Category: dhna]]
+
-
 
+
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:54:00 2008''
+

Current revision

DHNA complex with 8-Amino-1,3-dimethyl-3,7-dihydropurine-2,6-dione

PDB ID 1rs2

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1rs2"
Personal tools