View source for 6gy9


==Fucose-functionalized precision glycomacromolecules targeting human norovirus capsid protein==
<StructureSection load='6gy9' size='340' side='right' caption='[[6gy9]], [[Resolution|resolution]] 1.83&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6gy9]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Norwalk_calicivirus Norwalk calicivirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GY9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GY9 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=KBA:(2~{S},3~{S},4~{R},5~{S},6~{R})-2-methyl-6-[2-(1,2,3-triazol-1-yl)ethoxy]oxane-3,4,5-triol'>KBA</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=6gy9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gy9 OCA], [http://pdbe.org/6gy9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gy9 RCSB], [http://www.ebi.ac.uk/pdbsum/6gy9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gy9 ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Norovirus infection is the major cause of nonbacterial gastroenteritis in humans and has been the subject of numerous studies investigating the virus's biophysical properties and biochemical function with the aim of deriving novel and highly potent entry inhibitors to prevent infection. Recently, it has been shown that the protruding P domain dimer (P-dimer) of a GII.10 Norovirus strain exhibits two new binding sites for l-fucose in addition to the canonical binding sites. Thus, these sites provide a novel target for the design of multivalent fucose ligands as entry inhibitors of norovirus infections. In this current study, a first generation of multivalent fucose-functionalized glycomacromolecules was synthesized and applied as model structures to investigate the potential targeting of fucose binding sites in human norovirus P-dimer. Following previously established solid phase polymer synthesis, eight precision glycomacromolecules varying in number and position of fucose ligands along an oligo(amidoamine) backbone were obtained and then used in a series of binding studies applying native MS, NMR, and X-ray crystallography. We observed only one fucose per glycomacromolecule binding to one P-dimer resulting in similar binding affinities for all fucose-functionalized glycomacromolecules, which based on our current findings we attribute to the overall size of macromolecular ligands and possibly to steric hindrance.

Fucose-Functionalized Precision Glycomacromolecules Targeting Human Norovirus Capsid Protein.,Bucher KS, Yan H, Creutznacher R, Ruoff K, Mallagaray A, Grafmuller A, Dirks JS, Kilic T, Weickert S, Rubailo A, Drescher M, Schmidt S, Hansman G, Peters T, Uetrecht C, Hartmann L Biomacromolecules. 2018 Aug 16. doi: 10.1021/acs.biomac.8b00829. PMID:30071731<ref>PMID:30071731</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6gy9" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Norwalk calicivirus]]
[[Category: Hansman, G S]]
[[Category: Kilic, T]]
[[Category: Ruoff, K]]
[[Category: Fucose]]
[[Category: Gii 10]]
[[Category: Norovirus]]
[[Category: P domain]]
[[Category: Triazol]]
[[Category: Viral protein]]