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==Human galectin-3 in complex with a benzamido-N-acetyllactoseamine inhibitor==
==Human galectin-3 in complex with a benzamido-N-acetyllactoseamine inhibitor==
<StructureSection load='2xg3' size='340' side='right' caption='[[2xg3]], [[Resolution|resolution]] 1.20&Aring;' scene=''>
<StructureSection load='2xg3' size='340' side='right'caption='[[2xg3]], [[Resolution|resolution]] 1.20&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[2xg3]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XG3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2XG3 FirstGlance]. <br>
<table><tr><td colspan='2'>[[2xg3]] 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=2XG3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XG3 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GAL:BETA-D-GALACTOSE'>GAL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=UNU:BENZAMIDE'>UNU</scene></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]] 1.2&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1a3k|1a3k]], [[1kjr|1kjr]], [[1kjl|1kjl]]</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=GAL:BETA-D-GALACTOSE'>GAL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=UNU:BENZAMIDE'>UNU</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=2xg3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xg3 OCA], [http://pdbe.org/2xg3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2xg3 RCSB], [http://www.ebi.ac.uk/pdbsum/2xg3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2xg3 ProSAT]</span></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=2xg3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xg3 OCA], [https://pdbe.org/2xg3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xg3 RCSB], [https://www.ebi.ac.uk/pdbsum/2xg3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xg3 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://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>
[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 ==
Rational drug design is predicated on knowledge of the three-dimensional structure of the protein-ligand complex and the thermodynamics of ligand binding. Despite the fundamental importance of both enthalpy and entropy in driving ligand binding, the role of conformational entropy is rarely addressed in drug design. In this work, we have probed the conformational entropy and its relative contribution to the free energy of ligand binding to the carbohydrate recognition domain of galectin-3. Using a combination of NMR spectroscopy, isothermal titration calorimetry, and X-ray crystallography, we characterized the binding of three ligands with dissociation constants ranging over 2 orders of magnitude. (15)N and (2)H spin relaxation measurements showed that the protein backbone and side chains respond to ligand binding by increased conformational fluctuations, on average, that differ among the three ligand-bound states. Variability in the response to ligand binding is prominent in the hydrophobic core, where a distal cluster of methyl groups becomes more rigid, whereas methyl groups closer to the binding site become more flexible. The results reveal an intricate interplay between structure and conformational fluctuations in the different complexes that fine-tunes the affinity. The estimated change in conformational entropy is comparable in magnitude to the binding enthalpy, demonstrating that it contributes favorably and significantly to ligand binding. We speculate that the relatively weak inherent protein-carbohydrate interactions and limited hydrophobic effect associated with oligosaccharide binding might have exerted evolutionary pressure on carbohydrate-binding proteins to increase the affinity by means of conformational entropy.


Protein Flexibility and Conformational Entropy in Ligand Design Targeting the Carbohydrate Recognition Domain of Galectin-3.,Diehl C, Engstrom O, Delaine T, Hakansson M, Genheden S, Modig K, Leffler H, Ryde U, Nilsson UJ, Akke M J Am Chem Soc. 2010 Sep 28. PMID:20873837<ref>PMID:20873837</ref>
==See Also==
 
*[[Galectin 3D structures|Galectin 3D structures]]
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2xg3" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Akke, M]]
[[Category: Homo sapiens]]
[[Category: Delaine, T]]
[[Category: Large Structures]]
[[Category: Diehl, C]]
[[Category: Akke M]]
[[Category: Engstrom, O]]
[[Category: Delaine T]]
[[Category: Genheden, S]]
[[Category: Diehl C]]
[[Category: Hakansson, M]]
[[Category: Engstrom O]]
[[Category: Leffler, H]]
[[Category: Genheden S]]
[[Category: Modig, K]]
[[Category: Hakansson M]]
[[Category: Nilsson, U]]
[[Category: Leffler H]]
[[Category: Ryde, U]]
[[Category: Modig K]]
[[Category: Ige-binding protein]]
[[Category: Nilsson U]]
[[Category: Lectin]]
[[Category: Ryde U]]
[[Category: Sugar binding protein]]

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