View source for 1rsd


==DHNA complex with 3-(5-Amino-7-hydroxy-[1,2,3]triazolo[4,5-d]pyrimidin-2-yl)-N-[2-(2-hydroxymethyl-phenylsulfanyl)-benzyl]-benzamide==
<StructureSection load='1rsd' size='340' side='right' caption='[[1rsd]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1rsd]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"micrococcus_aureus"_(rosenbach_1884)_zopf_1885 "micrococcus aureus" (rosenbach 1884) zopf 1885]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RSD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1RSD FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PSB:3-(5-AMINO-7-HYDROXY-[1,2,3]TRIAZOLO[4,5-D]PYRIMIDIN-2-YL)-N-[2-(2-(HYDROXYMETHYL-PHENYLSULFANYL)-BENZYL]-BENZAMIDE'>PSB</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1rs4|1rs4]], [[1rs2|1rs2]], [[1rri|1rri]], [[1rry|1rry]], [[1rrw|1rrw]], [[1rr5|1rr5]], [[1rsi|1rsi]]</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">FOLB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1280 "Micrococcus aureus" (Rosenbach 1884) Zopf 1885])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1rsd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1rsd OCA], [http://pdbe.org/1rsd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1rsd RCSB], [http://www.ebi.ac.uk/pdbsum/1rsd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1rsd ProSAT]</span></td></tr>
</table>
== Function ==
[[http://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/1rsd_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=1rsd ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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.

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<ref>PMID:15027862</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 1rsd" style="background-color:#fffaf0;"></div>

==See Also==
*[[Aldolase|Aldolase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Dihydroneopterin aldolase]]
[[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: Magdalinos, P]]
[[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: Wagner, R]]
[[Category: Walter, K A]]
[[Category: 8-dihydroneopterin aldolase]]
[[Category: Dhna]]
[[Category: Lyase]]