8oji - Revision history

OCA at 11:21, 14 March 2024

OCA — Thu, 14 Mar 2024 11:21:01 GMT

←Older revision		Revision as of 11:21, 14 March 2024
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	== Function ==		== 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>		[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 is involved in multiple pathways of many diseases, including cancer, fibrosis, and diabetes, and it is a validated pharmaceutical target for the development of novel therapeutic agents to address unmet medical needs. Novel 1,2-thiodisaccharides with a C-glycosylic functionality were synthesized by the photoinitiated thiol-ene click reaction of O-peracylated 1-C-substituted glycals and 1-thio-glycopyranoses. Subsequent global deprotection yielded test compounds, which were studied for their binding to human galectin-3 by fluorescence polarization and isothermal titration calorimetry to show low micromolar K(d) values. The best inhibitor displayed a K(d) value of 8.0 muM. An analysis of the thermodynamic binding parameters revealed that the binding Gibbs free energy (DeltaG) of the new inhibitors was dominated by enthalpy (DeltaH). The binding mode of the four most efficient 1,2-thiodisaccharides was also studied by X-ray crystallography that uncovered the unique role of water-mediated hydrogen bonds in conferring enthalpy-driven affinity enhancement for the new inhibitors. This 1,2-thiodisaccharide-type scaffold represents a new lead for galectin-3 inhibitor discovery and offers several possibilities for further development.
-
-	Strong Binding of C-Glycosylic1,2-Thiodisaccharides to Galectin-3 horizontal line Enthalpy-Driven Affinity Enhancement by Water-Mediated Hydrogen Bonds.,Lazar L, Tsagkarakou AS, Stravodimos G, Kontopidis G, Leffler H, Nilsson UJ, Somsak L, Leonidas DD J Med Chem. 2023 Sep 14;66(17):12420-12431. doi: 10.1021/acs.jmedchem.3c00882. , Epub 2023 Sep 2. PMID:37658813<ref>PMID:37658813</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 8oji" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 18:18, 20 September 2023

OCA — Wed, 20 Sep 2023 18:18:34 GMT

←Older revision		Revision as of 18:18, 20 September 2023
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 8oji is ~~ON HOLD until Paper~~ Publication	+	==Galectin-3 in complex with Methyl 2,6-anhydro-3-deoxy-3-S-(b-D-galactopyranosyl)-3-thio-D-glycero-L-altro-heptonate==
		+	<StructureSection load='8oji' size='340' side='right'caption='[[8oji]], [[Resolution\|resolution]] 1.75Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[8oji]] 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=8OJI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8OJI 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]] 1.75Å</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=VPH:methyl+(2~{R},4~{R},5~{R},6~{R})-6-(hydroxymethyl)-4,5-bis(oxidanyl)oxane-2-carboxylate'>VPH</scene>, <scene name='pdbligand=YIO:(2R,3R,4S,5R,6S)-2-(HYDROXYMETHYL)-6-SULFANYL-OXANE-3,4,5-TRIOL'>YIO</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=8oji FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8oji OCA], [https://pdbe.org/8oji PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8oji RCSB], [https://www.ebi.ac.uk/pdbsum/8oji PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8oji 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 ==
		+	Galectin-3 is involved in multiple pathways of many diseases, including cancer, fibrosis, and diabetes, and it is a validated pharmaceutical target for the development of novel therapeutic agents to address unmet medical needs. Novel 1,2-thiodisaccharides with a C-glycosylic functionality were synthesized by the photoinitiated thiol-ene click reaction of O-peracylated 1-C-substituted glycals and 1-thio-glycopyranoses. Subsequent global deprotection yielded test compounds, which were studied for their binding to human galectin-3 by fluorescence polarization and isothermal titration calorimetry to show low micromolar K(d) values. The best inhibitor displayed a K(d) value of 8.0 muM. An analysis of the thermodynamic binding parameters revealed that the binding Gibbs free energy (DeltaG) of the new inhibitors was dominated by enthalpy (DeltaH). The binding mode of the four most efficient 1,2-thiodisaccharides was also studied by X-ray crystallography that uncovered the unique role of water-mediated hydrogen bonds in conferring enthalpy-driven affinity enhancement for the new inhibitors. This 1,2-thiodisaccharide-type scaffold represents a new lead for galectin-3 inhibitor discovery and offers several possibilities for further development.

-	~~Authors: Tsagkarakou~~, ~~A.S~~., ~~Leonidas~~, D.D.	+	Strong Binding of C-Glycosylic1,2-Thiodisaccharides to Galectin-3 horizontal line Enthalpy-Driven Affinity Enhancement by Water-Mediated Hydrogen Bonds.,Lazar L, Tsagkarakou AS, Stravodimos G, Kontopidis G, Leffler H, Nilsson UJ, Somsak L, Leonidas DD J Med Chem. 2023 Sep 14;66(17):12420-12431. doi: 10.1021/acs.jmedchem.3c00882. , Epub 2023 Sep 2. PMID:37658813<ref>PMID:37658813</ref>

-	~~Description: Galectin-3 in complex with Methyl 2~~,~~6-anhydro-3-deoxy-3-~~S-(b-~~D-galactopyranosyl)-3-thio-D-glycero-L-altro-heptonate~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
-	[[Category: ~~Tsagkarakou, A.S~~]]	+	<div class="pdbe-citations 8oji" style="background-color:#fffaf0;"></div>
-	[[Category: ~~Leonidas, D.D~~]]	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
		+	[[Category: Leonidas DD]]
		+	[[Category: Tsagkarakou AS]]

OCA: Protected "8oji" [edit=sysop:move=sysop]

OCA — Fri, 07 Apr 2023 05:08:41 GMT

Protected "8oji" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:08, 7 April 2023

OCA: New page: '''Unreleased structure''' The entry 8oji is ON HOLD until Paper Publication Authors: Tsagkarakou, A.S., Leonidas, D.D. Description: Galectin-3 in complex with Methyl 2,6-anhydro-3-deo...

OCA — Fri, 07 Apr 2023 05:08:40 GMT

New page: '''Unreleased structure''' The entry 8oji is ON HOLD until Paper Publication Authors: Tsagkarakou, A.S., Leonidas, D.D. Description: Galectin-3 in complex with Methyl 2,6-anhydro-3-deo...

New page

'''Unreleased structure'''

The entry 8oji is ON HOLD until Paper Publication

Authors: Tsagkarakou, A.S., Leonidas, D.D.

Description: Galectin-3 in complex with Methyl 2,6-anhydro-3-deoxy-3-S-(b-D-galactopyranosyl)-3-thio-D-glycero-L-altro-heptonate
[[Category: Unreleased Structures]]
[[Category: Tsagkarakou, A.S]]
[[Category: Leonidas, D.D]]