View source for 6tf6


==Human galectin-3c in complex with a galactose derivative==
<StructureSection load='6tf6' size='340' side='right'caption='[[6tf6]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6tf6]] is a 1 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=6TF6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6TF6 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]] 1.5&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=N62:~{N}-[[(2~{S},3~{S},4~{R},5~{S},6~{R})-4-[[5,6-bis(fluoranyl)-2-oxidanylidene-chromen-3-yl]methoxy]-6-(hydroxymethyl)-3,5-bis(oxidanyl)oxan-2-yl]methyl]-4-fluoranyl-naphthalene-1-carboxamide'>N62</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=6tf6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tf6 OCA], [https://pdbe.org/6tf6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6tf6 RCSB], [https://www.ebi.ac.uk/pdbsum/6tf6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6tf6 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/LEG3_HUMAN LEG3_HUMAN] Galactose-specific lectin which binds IgE. May mediate with the alpha-3, beta-1 integrin the stimulation by CSPG4 of endothelial cells migration. Together with DMBT1, required for terminal differentiation of columnar epithelial cells during early embryogenesis (By similarity). In the nucleus: acts as a pre-mRNA splicing factor. Involved in acute inflammatory responses including neutrophil activation and adhesion, chemoattraction of monocytes macrophages, opsonization of apoptotic neutrophils, and activation of mast cells.<ref>PMID:15181153</ref> <ref>PMID:19594635</ref> <ref>PMID:19616076</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The galectins are a family of galactose-binding proteins playing key roles in inflammatory processes and cancer. However, they are structurally very closely related, and discovery of highly selective inhibitors is challenging. In this work, we report the design of novel inhibitors binding to a subsite unique to galectin-3, which confers both high selectivity and affinity towards galectin-3. Olefin cross metathesis between allyl beta-C-galactopyranosyl and 1-vinylnaphthalenes or acylation of aminomethyl beta-C-galactopyranosyl with 1-naphthoic acid derivatives gave C-galactopyranosyls carrying 1-naphthamide structural elements that interacted favorably with a galectin-3 unique subsite according to molecular modeling and X-ray structural analysis of two inhibitor-galectin-3 complexes. Affinities were down to sub-microM and selectivities over galectin-1, 2, 4 N-terminal domain, 4 C-terminal domain, 7, 8 N-terminal domain, 9 N-terminal domain, and 9 C-terminal domain were high. These results show that high affinity and selectivity for a single galectin can be achieved by targeting unique subsites, which holds promise for further development of small and selective galectin inhibitors.

3-Substituted 1-Naphthamidomethyl-C-galactosyls Interact with Two Unique Sub-sites for High-Affinity and High-Selectivity Inhibition of Galectin-3.,Dahlqvist A, Mandal S, Peterson K, Hakansson M, Logan DT, Zetterberg FR, Leffler H, Nilsson UJ Molecules. 2019 Dec 12;24(24). pii: molecules24244554. doi:, 10.3390/molecules24244554. PMID:31842451<ref>PMID:31842451</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6tf6" style="background-color:#fffaf0;"></div>

==See Also==
*[[Galectin 3D structures|Galectin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Hakansson M]]
[[Category: Logan DT]]
[[Category: Nilsson UJ]]
[[Category: Zetterberg F]]