OCA at 16:18, 29 November 2023

OCA — Wed, 29 Nov 2023 16:18:20 GMT

←Older revision		Revision as of 16:18, 29 November 2023
Line 1:		Line 1:

	==Structure of human Galectin-3 CRD in complex with TD-139 belonging to P31 space group.==		==Structure of human Galectin-3 CRD in complex with TD-139 belonging to P31 space group.==
-	<StructureSection load='7cxa' size='340' side='right'caption='[[7cxa]]' scene=''>	+	<StructureSection load='7cxa' size='340' side='right'caption='[[7cxa]], [[Resolution\|resolution]] 1.97Å' 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=7CXA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CXA FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7cxa]] 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=7CXA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CXA FirstGlance]. <br>
-	</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=7cxa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7cxa OCA], [https://pdbe.org/7cxa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7cxa RCSB], [https://www.ebi.ac.uk/pdbsum/7cxa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7cxa ProSAT]</span></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]] 1.97Å</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=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=7cxa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7cxa OCA], [https://pdbe.org/7cxa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7cxa RCSB], [https://www.ebi.ac.uk/pdbsum/7cxa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7cxa ProSAT]</span></td></tr>
	</table>		</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 ==
		+	Galectin-3 (Gal-3), a beta-galactoside-binding lectin, has been implicated in a plethora of pathological disorders including fibrosis, inflammation, cancer and metabolic diseases. TD139-a thio-digalactoside inhibitor developed by Galecto Biotech as a potential therapeutic for idiopathic pulmonary fibrosis-is the most advanced small-molecule Gal-3 inhibitor in clinical studies. It binds to human Gal-3 with high affinity but has lower affinity towards mouse and rat homologs, which is also manifested in the differential inhibition of Gal-3 function. Using biophysical methods and high-resolution X-ray co-crystal structures of TD139 and Gal-3 proteins, we demonstrate that a single amino acid change corresponding to A146 in human Gal-3 is sufficient for the observed reduction in the binding affinity of TD139 in rodents. Site-directed mutagenesis of A146V (in human Gal-3) and V160A (in mouse Gal-3) was sufficient to interchange the affinities, mainly by affecting the off rates of the inhibitor binding. In addition, molecular dynamics simulations of both wild-type and mutant structures revealed the sustained favorable noncovalent interactions between the fluorophenyl ring and the active site A146 (human Gal-3 and mouse V160A) that corroborate the finding from biophysical studies. Current findings have ramifications in the context of optimization of drug candidates against Gal-3.
		+
		+	Molecular mechanism of interspecies differences in the binding affinity of TD139 to Galectin-3.,Kumar A, Paul M, Panda M, Jayaram S, Kalidindi N, Sale H, Vetrichelvan M, Gupta A, Mathur A, Beno B, Regueiro-Ren A, Cheng D, Ramarao M, Ghosh K Glycobiology. 2021 Nov 18;31(10):1390-1400. doi: 10.1093/glycob/cwab072. PMID:34228782<ref>PMID:34228782</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7cxa" 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: Kumar A]]		[[Category: Kumar A]]

OCA at 10:49, 16 February 2022

OCA — Wed, 16 Feb 2022 10:49:03 GMT

←Older revision		Revision as of 10:49, 16 February 2022
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-	'''Unreleased structure'''

-	~~The entry~~ 7cxa ~~is ON HOLD until Paper Publication~~	+	==Structure of human Galectin-3 CRD in complex with TD-139 belonging to P31 space group.==
-		+	<StructureSection load='7cxa' size='340' side='right'caption='[[7cxa]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7CXA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CXA FirstGlance]. <br>
-	~~Description~~:	+	</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=7cxa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7cxa OCA], [https://pdbe.org/7cxa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7cxa RCSB], [https://www.ebi.ac.uk/pdbsum/7cxa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7cxa ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Kumar A]]

OCA at 08:34, 19 May 2021

OCA — Wed, 19 May 2021 08:34:43 GMT

←Older revision		Revision as of 08:34, 19 May 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7cxa is ON HOLD	+	The entry 7cxa is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "7cxa" [edit=sysop:move=sysop]

OCA — Wed, 09 Sep 2020 07:34:36 GMT

Protected "7cxa" [edit=sysop:move=sysop]

←Older revision

Revision as of 07:34, 9 September 2020

OCA: New page: '''Unreleased structure''' The entry 7cxa is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 09 Sep 2020 07:34:33 GMT

New page: '''Unreleased structure''' The entry 7cxa is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7cxa is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]

7cxa - Revision history

OCA at 16:18, 29 November 2023

OCA at 10:49, 16 February 2022

OCA at 08:34, 19 May 2021

OCA: Protected "7cxa" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 7cxa is ON HOLD Authors: Description: Category: Unreleased Structures