6w4z: Difference between revisions
No edit summary |
No edit summary |
||
| (One intermediate revision by the same user not shown) | |||
| Line 1: | Line 1: | ||
==Galectin-8N terminal domain in complex with Methyl 3-O-[3-O-benzyloxy]-malonyl-beta-D-galactopyranoside== | ==Galectin-8N terminal domain in complex with Methyl 3-O-[3-O-benzyloxy]-malonyl-beta-D-galactopyranoside== | ||
<StructureSection load='6w4z' size='340' side='right'caption='[[6w4z]]' scene=''> | <StructureSection load='6w4z' size='340' side='right'caption='[[6w4z]], [[Resolution|resolution]] 1.59Å' 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=6W4Z OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[6w4z]] 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=6W4Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6W4Z FirstGlance]. <br> | ||
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.59Å</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=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=SZS:methyl+3-O-[3-(benzyloxy)-3-oxopropanoyl]-beta-D-galactopyranoside'>SZS</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=6w4z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6w4z OCA], [https://pdbe.org/6w4z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6w4z RCSB], [https://www.ebi.ac.uk/pdbsum/6w4z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6w4z ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/LEG8_HUMAN LEG8_HUMAN] Lectin with a marked preference for 3'-O-sialylated and 3'-O-sulfated glycans.<ref>PMID:21288902</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Galectin-8 is a beta-galactoside recognising protein having an important role in the regulation of bone remodeling, cancer progression and metastasis. Methyl-beta-D-galactopyranoside malonyl aromatic esters have been designed to target and engage with particular amino acid residues of the galectin-8N extended carbohydrate-binding site. The chemically synthesized compounds had in vitro binding affinity towards galectin-8N in the range of 5-33 muM, as evaluated by isothermal titration calorimetry. This affinity directly correlated with the compounds' ability to inhibit galectin-8-induced expression of chemokines and proinflammatory cytokines in SUM159 breast cancer cell line. X-ray crystallographic structure determination revealed that these monosaccharide-based compounds bind galectin-8N by engaging its unique arginine (Arg59), and simultaneously cross-linking to another (Arg45) located across the carbohydrate-binding site. This structure-based drug design approach has led to discovery of novel monosaccharide galactose-based antagonists, with the strongest binding compound (Kd 5.72 microM) being 7-fold tighter than the disaccharide lactose. | |||
Rational design and synthesis of methyl-beta-D-galactomalonyl phenyl esters as potent galectin-8N antagonists.,Patel B, Kishor C, Houston TA, Shatz-Azoulay H, Zick Y, Vinik Y, Blanchard H J Med Chem. 2020 Aug 18. doi: 10.1021/acs.jmedchem.0c00602. PMID:32809817<ref>PMID:32809817</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6w4z" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Galectin 3D structures|Galectin 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Blanchard H]] | [[Category: Blanchard H]] | ||
[[Category: Kishor C]] | [[Category: Kishor C]] | ||
[[Category: Patel B]] | [[Category: Patel B]] | ||
Latest revision as of 17:16, 18 October 2023
Galectin-8N terminal domain in complex with Methyl 3-O-[3-O-benzyloxy]-malonyl-beta-D-galactopyranosideGalectin-8N terminal domain in complex with Methyl 3-O-[3-O-benzyloxy]-malonyl-beta-D-galactopyranoside
Structural highlights
FunctionLEG8_HUMAN Lectin with a marked preference for 3'-O-sialylated and 3'-O-sulfated glycans.[1] Publication Abstract from PubMedGalectin-8 is a beta-galactoside recognising protein having an important role in the regulation of bone remodeling, cancer progression and metastasis. Methyl-beta-D-galactopyranoside malonyl aromatic esters have been designed to target and engage with particular amino acid residues of the galectin-8N extended carbohydrate-binding site. The chemically synthesized compounds had in vitro binding affinity towards galectin-8N in the range of 5-33 muM, as evaluated by isothermal titration calorimetry. This affinity directly correlated with the compounds' ability to inhibit galectin-8-induced expression of chemokines and proinflammatory cytokines in SUM159 breast cancer cell line. X-ray crystallographic structure determination revealed that these monosaccharide-based compounds bind galectin-8N by engaging its unique arginine (Arg59), and simultaneously cross-linking to another (Arg45) located across the carbohydrate-binding site. This structure-based drug design approach has led to discovery of novel monosaccharide galactose-based antagonists, with the strongest binding compound (Kd 5.72 microM) being 7-fold tighter than the disaccharide lactose. Rational design and synthesis of methyl-beta-D-galactomalonyl phenyl esters as potent galectin-8N antagonists.,Patel B, Kishor C, Houston TA, Shatz-Azoulay H, Zick Y, Vinik Y, Blanchard H J Med Chem. 2020 Aug 18. doi: 10.1021/acs.jmedchem.0c00602. PMID:32809817[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||