4y24: Difference between revisions
No edit summary |
No edit summary |
||
| Line 3: | Line 3: | ||
<StructureSection load='4y24' size='340' side='right'caption='[[4y24]], [[Resolution|resolution]] 2.32Å' scene=''> | <StructureSection load='4y24' size='340' side='right'caption='[[4y24]], [[Resolution|resolution]] 2.32Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4y24]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4y24]] 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=4Y24 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4Y24 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=TD2:3-DEOXY-3-[4-(3-FLUOROPHENYL)-1H-1,2,3-TRIAZOL-1-YL]-BETA-D-GALACTOPYRANOSYL+3-DEOXY-3-[4-(3-FLUOROPHENYL)-1H-1,2,3-TRIAZOL-1-YL]-1-THIO-BETA-D-GALACTOPYRANOSIDE'>TD2</scene> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=TD2:3-DEOXY-3-[4-(3-FLUOROPHENYL)-1H-1,2,3-TRIAZOL-1-YL]-BETA-D-GALACTOPYRANOSYL+3-DEOXY-3-[4-(3-FLUOROPHENYL)-1H-1,2,3-TRIAZOL-1-YL]-1-THIO-BETA-D-GALACTOPYRANOSIDE'>TD2</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=4y24 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4y24 OCA], [https://pdbe.org/4y24 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4y24 RCSB], [https://www.ebi.ac.uk/pdbsum/4y24 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4y24 ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/LEG1_HUMAN LEG1_HUMAN] May regulate apoptosis, cell proliferation and cell differentiation. Binds beta-galactoside and a wide array of complex carbohydrates. Inhibits CD45 protein phosphatase activity and therefore the dephosphorylation of Lyn kinase.<ref>PMID:14617626</ref> <ref>PMID:18796645</ref> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 22: | Line 20: | ||
==See Also== | ==See Also== | ||
*[[Galectin|Galectin]] | *[[Galectin 3D structures|Galectin 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Hsieh | [[Category: Hsieh TJ]] | ||
[[Category: Lin | [[Category: Lin CH]] | ||
[[Category: Lin | [[Category: Lin HY]] | ||
Revision as of 21:03, 26 April 2023
Complex of human Galectin-1 and TD-139Complex of human Galectin-1 and TD-139
Structural highlights
FunctionLEG1_HUMAN May regulate apoptosis, cell proliferation and cell differentiation. Binds beta-galactoside and a wide array of complex carbohydrates. Inhibits CD45 protein phosphatase activity and therefore the dephosphorylation of Lyn kinase.[1] [2] Publication Abstract from PubMedHuman galectins are promising targets for cancer immunotherapeutic and fibrotic disease-related drugs. We report herein the binding interactions of three thio-digalactosides (TDGs) including TDG itself, TD139 (3,3'-deoxy-3,3'-bis-(4-[m-fluorophenyl]-1H-1,2,3-triazol-1-yl)-thio-digalactosid e, recently approved for the treatment of idiopathic pulmonary fibrosis), and TAZTDG (3-deoxy-3-(4-[m-fluorophenyl]-1H-1,2,3-triazol-1-yl)-thio-digalactoside) with human galectins-1, -3 and -7 as assessed by X-ray crystallography, isothermal titration calorimetry and NMR spectroscopy. Five binding subsites (A-E) make up the carbohydrate-recognition domains of these galectins. We identified novel interactions between an arginine within subsite E of the galectins and an arene group in the ligands. In addition to the interactions contributed by the galactosyl sugar residues bound at subsites C and D, the fluorophenyl group of TAZTDG preferentially bound to subsite B in galectin-3, whereas the same group favored binding at subsite E in galectins-1 and -7. The characterised dual binding modes demonstrate how binding potency, reported as decreased Kd values of the TDG inhibitors from muM to nM, is improved and also offer insights to development of selective inhibitors for individual galectins. Dual thio-digalactoside-binding modes of human galectins as the structural basis for the design of potent and selective inhibitors.,Hsieh TJ, Lin HY, Tu Z, Lin TC, Wu SC, Tseng YY, Liu FT, Hsu ST, Lin CH Sci Rep. 2016 Jul 15;6:29457. doi: 10.1038/srep29457. PMID:27416897[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||