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[[ | ==Dihydropteroate Synthase in complex with DHP-STZ== | ||
<StructureSection load='3tye' size='340' side='right' caption='[[3tye]], [[Resolution|resolution]] 2.30Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3tye]] is a 2 chain structure with sequence from [http://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=3TYE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TYE 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>, <scene name='pdbligand=XHP:2-AMINO-6-METHYLIDENE-6,7-DIHYDROPTERIDIN-4(3H)-ONE'>XHP</scene>, <scene name='pdbligand=XTZ:4-{[(2-AMINO-4-OXO-3,4,7,8-TETRAHYDROPTERIDIN-6-YL)METHYL]AMINO}-N-(1,3-THIAZOL-2-YL)BENZENESULFONAMIDE'>XTZ</scene>, <scene name='pdbligand=YTZ:4-AMINO-N-(1,3-THIAZOL-2-YL)BENZENESULFONAMIDE'>YTZ</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1tws|1tws]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">folP, BAS0071, BA_0071, GBAA_0071 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=191218 Bacillus anthracis str. A2012])</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=3tye FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tye OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3tye RCSB], [http://www.ebi.ac.uk/pdbsum/3tye PDBsum]</span></td></tr> | |||
</table> | |||
<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> | |||
==See Also== | ==See Also== | ||
*[[Dihydropteroate synthase|Dihydropteroate synthase]] | *[[Dihydropteroate synthase|Dihydropteroate synthase]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: Bacillus anthracis str. a2012]] | [[Category: Bacillus anthracis str. a2012]] | ||
[[Category: Dihydropteroate synthase]] | [[Category: Dihydropteroate synthase]] | ||
[[Category: White, S W | [[Category: White, S W]] | ||
[[Category: Yun, M K | [[Category: Yun, M K]] | ||
[[Category: Anthracis]] | [[Category: Anthracis]] | ||
[[Category: Dihydropteroate]] | [[Category: Dihydropteroate]] | ||
Revision as of 19:57, 9 December 2014
Dihydropteroate Synthase in complex with DHP-STZDihydropteroate Synthase in complex with DHP-STZ
Structural highlights
Publication Abstract from PubMedThe 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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