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==Structural Studies of Pterin-Based Inhibitors of Dihydropteroate Synthase== | |||
<StructureSection load='3h2c' size='340' side='right'caption='[[3h2c]], [[Resolution|resolution]] 2.60Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3h2c]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_anthracis_str._A2012 Bacillus anthracis str. A2012]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3H2C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3H2C 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]] 2.6Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=B58:1H-IMIDAZO[4,5-D]PYRIDAZINE-4,7-DIAMINE'>B58</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=3h2c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3h2c OCA], [https://pdbe.org/3h2c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3h2c RCSB], [https://www.ebi.ac.uk/pdbsum/3h2c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3h2c ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q81VW8_BACAN Q81VW8_BACAN] | |||
== 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/h2/3h2c_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=3h2c ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Dihydropteroate synthase (DHPS) is a key enzyme in bacterial folate synthesis and the target of the sulfonamide class of antibacterials. Resistance and toxicities associated with sulfonamides have led to a decrease in their clinical use. Compounds that bind to the pterin binding site of DHPS, as opposed to the p-amino benzoic acid (pABA) binding site targeted by the sulfonamide agents, are anticipated to bypass sulfonamide resistance. To identify such inhibitors and map the pterin binding pocket, we have performed virtual screening, synthetic, and structural studies using Bacillus anthracis DHPS. Several compounds with inhibitory activity have been identified, and crystal structures have been determined that show how the compounds engage the pterin site. The structural studies identify the key binding elements and have been used to generate a structure-activity based pharmacophore map that will facilitate the development of the next generation of DHPS inhibitors which specifically target the pterin site. | |||
Structural Studies of Pterin-Based Inhibitors of Dihydropteroate Synthase.,Hevener KE, Yun MK, Qi J, Kerr ID, Babaoglu K, Hurdle JG, Balakrishna K, White SW, Lee RE J Med Chem. 2009 Nov 9. PMID:19899766<ref>PMID:19899766</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3h2c" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[Dihydropteroate synthase|Dihydropteroate synthase]] | *[[Dihydropteroate synthase 3D structures|Dihydropteroate synthase 3D structures]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
[[Category: Bacillus anthracis str. | </StructureSection> | ||
[[Category: | [[Category: Bacillus anthracis str. A2012]] | ||
[[Category: White | [[Category: Large Structures]] | ||
[[Category: Yun | [[Category: White SW]] | ||
[[Category: Yun M-K]] | |||
Latest revision as of 10:15, 6 September 2023
Structural Studies of Pterin-Based Inhibitors of Dihydropteroate SynthaseStructural Studies of Pterin-Based Inhibitors of Dihydropteroate Synthase
Structural highlights
FunctionEvolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedDihydropteroate synthase (DHPS) is a key enzyme in bacterial folate synthesis and the target of the sulfonamide class of antibacterials. Resistance and toxicities associated with sulfonamides have led to a decrease in their clinical use. Compounds that bind to the pterin binding site of DHPS, as opposed to the p-amino benzoic acid (pABA) binding site targeted by the sulfonamide agents, are anticipated to bypass sulfonamide resistance. To identify such inhibitors and map the pterin binding pocket, we have performed virtual screening, synthetic, and structural studies using Bacillus anthracis DHPS. Several compounds with inhibitory activity have been identified, and crystal structures have been determined that show how the compounds engage the pterin site. The structural studies identify the key binding elements and have been used to generate a structure-activity based pharmacophore map that will facilitate the development of the next generation of DHPS inhibitors which specifically target the pterin site. Structural Studies of Pterin-Based Inhibitors of Dihydropteroate Synthase.,Hevener KE, Yun MK, Qi J, Kerr ID, Babaoglu K, Hurdle JG, Balakrishna K, White SW, Lee RE J Med Chem. 2009 Nov 9. PMID:19899766[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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