5oa6
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of ScGas2 in complex with compound 12== | |
| + | <StructureSection load='5oa6' size='340' side='right' caption='[[5oa6]], [[Resolution|resolution]] 1.94Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5oa6]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OA6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5OA6 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9PT:(2~{R},3~{S},4~{S},5~{R},6~{S})-2-(hydroxymethyl)-6-[(2~{R},3~{R},4~{S},5~{R},6~{S})-2-(hydroxymethyl)-6-[(2~{R},3~{R},4~{S},5~{R},6~{R})-2-(hydroxymethyl)-3,5-bis(oxidanyl)-6-[4-(3-quinolin-1-ium-1-ylpropyl)-1,2,3-triazol-1-yl]oxan-4-yl]oxy-3,5-bis(oxidanyl)oxan-4-yl]oxy-oxane-3,4,5-triol'>9PT</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5oa6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5oa6 OCA], [http://pdbe.org/5oa6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5oa6 RCSB], [http://www.ebi.ac.uk/pdbsum/5oa6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5oa6 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/GAS2_YEAST GAS2_YEAST]] Splits internally a 1,3-beta-glucan molecule and transfers the newly generated reducing end (the donor) to the non-reducing end of another 1,3-beta-glucan molecule (the acceptor) forming a 1,3-beta linkage, resulting in the elongation of 1,3-beta-glucan chains in the cell wall. Involved in spore wall assembly.<ref>PMID:17189486</ref> <ref>PMID:17397106</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Fungal beta-1,3-glucan glucanosyltransferases are glucan-remodeling enzymes that play important roles in cell wall integrity, and are essential for the viability of pathogenic fungi and yeasts. As such, they are considered possible drug targets, although inhibitors of this class of enzymes have not yet been reported. Herein we report a multidisciplinary approach based on a structure-guided design using a highly conserved transglycosylase from Sacharomyces cerevisiae, that leads to carbohydrate derivatives with high affinity for Aspergillus fumigatus Gel4. We demonstrate by X-ray crystallography that the compounds bind in the active site of Gas2/Gel4 and interact with the catalytic machinery. The topological analysis of noncovalent interactions demonstrates that the combination of a triazole with positively charged aromatic moieties are important for optimal interactions with Gas2/Gel4 through unusual pyridinium cation-pi and face-to-face pi-pi interactions. The lead compound is capable of inhibiting AfGel4 with an IC50 value of 42 mum. | ||
| - | + | Inhibitors against Fungal Cell Wall Remodeling Enzymes.,Delso I, Valero-Gonzalez J, Gomollon-Bel F, Castro-Lopez J, Fang W, Navratilova I, van Aalten DMF, Tejero T, Merino P, Hurtado-Guerrero R ChemMedChem. 2018 Jan 22;13(2):128-132. doi: 10.1002/cmdc.201700720. Epub 2017, Dec 12. PMID:29164827<ref>PMID:29164827</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 5oa6" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Aalten, D Van]] | ||
| + | [[Category: Castro-Lopez, J]] | ||
[[Category: Delso, I]] | [[Category: Delso, I]] | ||
[[Category: Fang, W]] | [[Category: Fang, W]] | ||
| - | [[Category: | + | [[Category: Gomollon-Bel, F]] |
| - | + | ||
| - | + | ||
| - | + | ||
[[Category: Hurtado-Guerrero, R]] | [[Category: Hurtado-Guerrero, R]] | ||
[[Category: Merino, P]] | [[Category: Merino, P]] | ||
[[Category: Navratilova, I]] | [[Category: Navratilova, I]] | ||
| - | [[Category: | + | [[Category: Tejero, T]] |
| + | [[Category: Valero-Gonzalez, J]] | ||
| + | [[Category: Transferase]] | ||
Revision as of 07:58, 2 May 2018
Crystal structure of ScGas2 in complex with compound 12
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