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| ==Structural and Mechanistic Studies of Catalysis and Sulfa Drug Resistance in Dihydropteroate Synthase== | | ==Structural and Mechanistic Studies of Catalysis and Sulfa Drug Resistance in Dihydropteroate Synthase== |
| <StructureSection load='3v5o' size='340' side='right' caption='[[3v5o]], [[Resolution|resolution]] 2.50Å' scene=''> | | <StructureSection load='3v5o' size='340' side='right'caption='[[3v5o]], [[Resolution|resolution]] 2.50Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[3v5o]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Bacaa Bacaa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3V5O OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3V5O FirstGlance]. <br> | | <table><tr><td colspan='2'>[[3v5o]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_anthracis_str._A0248 Bacillus anthracis str. A0248]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3V5O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3V5O FirstGlance]. <br> |
| </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5Å</td></tr> |
| <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1tws|1tws]]</td></tr>
| | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">folP, BAA_0084 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=592021 BACAA])</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=3v5o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3v5o OCA], [https://pdbe.org/3v5o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3v5o RCSB], [https://www.ebi.ac.uk/pdbsum/3v5o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3v5o ProSAT]</span></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>
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| <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=3v5o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3v5o OCA], [http://pdbe.org/3v5o PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3v5o RCSB], [http://www.ebi.ac.uk/pdbsum/3v5o PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3v5o ProSAT]</span></td></tr> | |
| </table> | | </table> |
| == Function ==
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| [[http://www.uniprot.org/uniprot/C3P9L8_BACAA C3P9L8_BACAA]] DHPS catalyzes the formation of the immediate precursor of folic acid.[RuleBase:RU361205]
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| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| 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.
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| 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>
| | ==See Also== |
| | | *[[Dihydropteroate synthase 3D structures|Dihydropteroate synthase 3D structures]] |
| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 3v5o" style="background-color:#fffaf0;"></div>
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| == References == | |
| <references/>
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Bacaa]] | | [[Category: Bacillus anthracis str. A0248]] |
| [[Category: Dihydropteroate synthase]] | | [[Category: Large Structures]] |
| [[Category: Bashford, D]] | | [[Category: Bashford D]] |
| [[Category: Ferreira, A M]] | | [[Category: Ferreira AM]] |
| [[Category: Lee, R E]] | | [[Category: Lee RE]] |
| [[Category: Li, Z]] | | [[Category: Li Z]] |
| [[Category: Waddell, M B]] | | [[Category: Waddell MB]] |
| [[Category: White, S W]] | | [[Category: White SW]] |
| [[Category: Wu, Y]] | | [[Category: Wu Y]] |
| [[Category: Yun, M]] | | [[Category: Yun M]] |
| [[Category: Zhao, Y]] | | [[Category: Zhao Y]] |
| [[Category: Dhpp and paba]]
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| [[Category: Tim barrel]]
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| [[Category: Transferase]]
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