3tzf
From Proteopedia
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| - | [[ | + | ==Crystal Structure of the Yersinia pestis Dihydropteroate Synthase with Sulfonamide Drug Complex.== |
| + | <StructureSection load='3tzf' size='340' side='right' caption='[[3tzf]], [[Resolution|resolution]] 2.10Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[3tzf]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Yersinia_pestis Yersinia pestis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TZF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TZF FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=08D:SULFAMETHOXAZOLE'>08D</scene>, <scene name='pdbligand=HH2:6-HYDROXYMETHYLPTERIN-DIPHOSPHATE'>HH2</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3tyu|3tyu]], [[3tyz|3tyz]], [[3tzn|3tzn]]</td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">dhpS, folP, y0683, YPO3501, YP_0582 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=632 Yersinia pestis])</td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dihydropteroate_synthase Dihydropteroate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.15 2.5.1.15] </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=3tzf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tzf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3tzf RCSB], [http://www.ebi.ac.uk/pdbsum/3tzf PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/Q7CKJ1_YERPE Q7CKJ1_YERPE]] DHPS catalyzes the formation of the immediate precursor of folic acid.[RuleBase:RU361205] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The sulfonamide antibiotics inhibit dihydropteroate synthase (DHPS), a key enzyme in the folate pathway of bacteria and primitive eukaryotes. However, resistance mutations have severely compromised the usefulness of these drugs. We report structural, computational, and mutagenesis studies on the catalytic and resistance mechanisms of DHPS. By performing the enzyme-catalyzed reaction in crystalline DHPS, we have structurally characterized key intermediates along the reaction pathway. Results support an S(N)1 reaction mechanism via formation of a novel cationic pterin intermediate. We also show that two conserved loops generate a substructure during catalysis that creates a specific binding pocket for p-aminobenzoic acid, one of the two DHPS substrates. This substructure, together with the pterin-binding pocket, explains the roles of the conserved active-site residues and reveals how sulfonamide resistance arises. | ||
| - | + | Catalysis and sulfa drug resistance in dihydropteroate synthase.,Yun MK, Wu Y, Li Z, Zhao Y, Waddell MB, Ferreira AM, Lee RE, Bashford D, White SW Science. 2012 Mar 2;335(6072):1110-4. PMID:22383850<ref>PMID:22383850</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
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==See Also== | ==See Also== | ||
*[[Dihydropteroate synthase|Dihydropteroate synthase]] | *[[Dihydropteroate synthase|Dihydropteroate synthase]] | ||
| - | + | == References == | |
| - | == | + | <references/> |
| - | < | + | __TOC__ |
| + | </StructureSection> | ||
[[Category: Dihydropteroate synthase]] | [[Category: Dihydropteroate synthase]] | ||
[[Category: Yersinia pestis]] | [[Category: Yersinia pestis]] | ||
| - | [[Category: Wu, Y | + | [[Category: Wu, Y]] |
| - | + | ||
[[Category: Sulfonamide complex]] | [[Category: Sulfonamide complex]] | ||
[[Category: Tim barrel]] | [[Category: Tim barrel]] | ||
[[Category: Transferase-antibiotic-inhibitor complex]] | [[Category: Transferase-antibiotic-inhibitor complex]] | ||
[[Category: Transferase-inhibitor-antibiotic complex]] | [[Category: Transferase-inhibitor-antibiotic complex]] | ||
Revision as of 08:05, 15 February 2015
Crystal Structure of the Yersinia pestis Dihydropteroate Synthase with Sulfonamide Drug Complex.
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