5o9p

From Proteopedia

(Difference between revisions)

Revision as of 12:19, 26 August 2020

Crystal structure of Gas2 in complex with compound 10

Structural highlights

5o9p is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1] ^[2]

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^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Ragni E, Coluccio A, Rolli E, Rodriguez-Pena JM, Colasante G, Arroyo J, Neiman AM, Popolo L. GAS2 and GAS4, a pair of developmentally regulated genes required for spore wall assembly in Saccharomyces cerevisiae. Eukaryot Cell. 2007 Feb;6(2):302-16. Epub 2006 Dec 22. PMID:17189486 doi:http://dx.doi.org/EC.00321-06
↑ Ragni E, Fontaine T, Gissi C, Latge JP, Popolo L. The Gas family of proteins of Saccharomyces cerevisiae: characterization and evolutionary analysis. Yeast. 2007 Apr;24(4):297-308. PMID:17397106 doi:http://dx.doi.org/10.1002/yea.1473
↑ 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. Inhibitors against Fungal Cell Wall Remodeling Enzymes. ChemMedChem. 2018 Jan 22;13(2):128-132. doi: 10.1002/cmdc.201700720. Epub 2017, Dec 12. PMID:29164827 doi:http://dx.doi.org/10.1002/cmdc.201700720

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5o9p"

@@ Line 1: / Line 1: @@
 ==Crystal structure of Gas2 in complex with compound 10==
-<StructureSection load='5o9p' size='340' side='right' caption='[[5o9p]], [[Resolution|resolution]] 1.75&Aring;' scene=''>
+<StructureSection load='5o9p' size='340' side='right'caption='[[5o9p]], [[Resolution|resolution]] 1.75&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5o9p]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5O9P OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5O9P FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5o9p]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5O9P OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5O9P FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9P8:(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-(pyridin-2-ylmethoxymethyl)-1,2,3-triazol-1-yl]oxan-4-yl]oxy-3,5-bis(oxidanyl)oxan-4-yl]oxy-oxane-3,4,5-triol'>9P8</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9P8:(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-(pyridin-2-ylmethoxymethyl)-1,2,3-triazol-1-yl]oxan-4-yl]oxy-3,5-bis(oxidanyl)oxan-4-yl]oxy-oxane-3,4,5-triol'>9P8</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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=5o9p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5o9p OCA], [http://pdbe.org/5o9p PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5o9p RCSB], [http://www.ebi.ac.uk/pdbsum/5o9p PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5o9p ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5o9p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5o9p OCA], [http://pdbe.org/5o9p PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5o9p RCSB], [http://www.ebi.ac.uk/pdbsum/5o9p PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5o9p ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 22: / Line 22: @@
 __TOC__
 </StructureSection>
+[[Category: Large Structures]]
 [[Category: Aalten, D Van]]
 [[Category: Castro-Lopez, J]]

5o9p

From Proteopedia

Revision as of 12:19, 26 August 2020

Crystal structure of Gas2 in complex with compound 10

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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