View source for 6vto


==Crystal structure of human Galectin-7 in complex with 4-O-beta-D-Galactopyranosyl-D-glucose==
<StructureSection load='6vto' size='340' side='right'caption='[[6vto]], [[Resolution|resolution]] 1.69&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6vto]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VTO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VTO FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.69&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LBL:(2~{R},3~{R},4~{R},5~{R})-4-[(2~{S},3~{R},4~{S},5~{R},6~{R})-6-(hydroxymethyl)-3,4,5-tris(oxidanyl)oxan-2-yl]oxy-2,3,5,+6-tetrakis(oxidanyl)hexanal'>LBL</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=6vto FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vto OCA], [https://pdbe.org/6vto PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vto RCSB], [https://www.ebi.ac.uk/pdbsum/6vto PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vto ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/LEG7_HUMAN LEG7_HUMAN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The design of allosteric modulators to control protein function is a key objective in drug discovery programs. Altering functionally essential allosteric residue networks provides unique protein family subtype specificity, minimizes unwanted off-target effects, and helps avert resistance acquisition typically plaguing drugs that target orthosteric sites. In this work, we used protein engineering and dimer interface mutations to positively and negatively modulate the immunosuppressive activity of the proapoptotic human galectin-7 (GAL-7). Using the PoPMuSiC and BeAtMuSiC algorithms, mutational sites and residue identity were computationally probed and predicted to either alter or stabilize the GAL-7 dimer interface. By designing a covalent disulfide bridge between protomers to control homodimer strength and stability, we demonstrate the importance of dimer interface perturbations on the allosteric network bridging the two opposite glycan-binding sites on GAL-7, resulting in control of induced apoptosis in Jurkat T cells. Molecular investigation of G16X GAL-7 variants using X-ray crystallography, biophysical, and computational characterization illuminates residues involved in dimer stability and allosteric communication, along with discrete long-range dynamic behaviors involving loops 1, 3, and 5. We show that perturbing the protein-protein interface between GAL-7 protomers can modulate its biological function, even when the overall structure and ligand-binding affinity remains unaltered. This study highlights new avenues for the design of galectin-specific modulators influencing both glycan-dependent and glycan-independent interactions.

Perturbing dimer interactions and allosteric communication modulates the immunosuppressive activity of human galectin-7.,Pham NTH, Letourneau M, Fortier M, Begin G, Al-Abdul-Wahid MS, Pucci F, Folch B, Rooman M, Chatenet D, St-Pierre Y, Lague P, Calmettes C, Doucet N J Biol Chem. 2021 Oct 19;297(5):101308. doi: 10.1016/j.jbc.2021.101308. PMID:34673030<ref>PMID:34673030</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6vto" style="background-color:#fffaf0;"></div>

==See Also==
*[[Galectin 3D structures|Galectin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Calmettes C]]
[[Category: Doucet N]]
[[Category: Pham NTH]]