6z7e
From Proteopedia
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==Variant Surface Glycoprotein VSGsur mutant H122A soaked in 7.7 mM suramin== | ==Variant Surface Glycoprotein VSGsur mutant H122A soaked in 7.7 mM suramin== | ||
| - | <StructureSection load='6z7e' size='340' side='right'caption='[[6z7e]]' scene=''> | + | <StructureSection load='6z7e' size='340' side='right'caption='[[6z7e]], [[Resolution|resolution]] 1.66Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6Z7E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6Z7E FirstGlance]. <br> | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6Z7E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6Z7E FirstGlance]. <br> | ||
| - | </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=6z7e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6z7e OCA], [https://pdbe.org/6z7e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6z7e RCSB], [https://www.ebi.ac.uk/pdbsum/6z7e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6z7e ProSAT]</span></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]] 1.663Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=6z7e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6z7e OCA], [https://pdbe.org/6z7e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6z7e RCSB], [https://www.ebi.ac.uk/pdbsum/6z7e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6z7e ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Suramin has been a primary early-stage treatment for African trypanosomiasis for nearly 100 yr. Recent studies revealed that trypanosome strains that express the variant surface glycoprotein (VSG) VSGsur possess heightened resistance to suramin. Here, we show that VSGsur binds tightly to suramin but other VSGs do not. By solving high-resolution crystal structures of VSGsur and VSG13, we also demonstrate that these VSGs define a structurally divergent subgroup of the coat proteins. The co-crystal structure of VSGsur with suramin reveals that the chemically symmetric drug binds within a large cavity in the VSG homodimer asymmetrically, primarily through contacts of its central benzene rings. Structure-based, loss-of-contact mutations in VSGsur significantly decrease the affinity to suramin and lead to a loss of the resistance phenotype. Altogether, these data show that the resistance phenotype is dependent on the binding of suramin to VSGsur, establishing that the VSG proteins can possess functionality beyond their role in antigenic variation. | ||
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| + | Structure of trypanosome coat protein VSGsur and function in suramin resistance.,Zeelen J, van Straaten M, Verdi J, Hempelmann A, Hashemi H, Perez K, Jeffrey PD, Halg S, Wiedemar N, Maser P, Papavasiliou FN, Stebbins CE Nat Microbiol. 2021 Mar;6(3):392-400. doi: 10.1038/s41564-020-00844-1. Epub 2021 , Jan 18. PMID:33462435<ref>PMID:33462435</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6z7e" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Current revision
Variant Surface Glycoprotein VSGsur mutant H122A soaked in 7.7 mM suramin
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