6qge - Revision history

OCA at 12:00, 24 January 2024

OCA — Wed, 24 Jan 2024 12:00:11 GMT

←Older revision		Revision as of 12:00, 24 January 2024
Line 1:		Line 1:

	==Galectin-3C in complex with a pair of enantiomeric ligands: S enantiomer==		==Galectin-3C in complex with a pair of enantiomeric ligands: S enantiomer==
-	<StructureSection load='6qge' size='340' side='right' caption='[[6qge]], [[Resolution\|resolution]] 1.16Å' scene=''>	+	<StructureSection load='6qge' size='340' side='right'caption='[[6qge]], [[Resolution\|resolution]] 1.16Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6qge]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QGE OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6QGE FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6qge]] 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=6QGE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6QGE FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=J1E:(2~{S},3~{R},4~{S},5~{R},6~{R})-4-[4-(3-fluorophenyl)-1,2,3-triazol-1-yl]-2-[(2~{S})-3-[4-(3-fluorophenyl)-1,2,3-triazol-1-yl]-2-oxidanyl-propyl]sulfanyl-6-(hydroxymethyl)oxane-3,5-diol'>J1E</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]] 1.16Å</td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">LGALS3, MAC2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])~~</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=J1E:(2~{S},3~{R},4~{S},5~{R},6~{R})-4-[4-(3-fluorophenyl)-1,2,3-triazol-1-yl]-2-[(2~{S})-3-[4-(3-fluorophenyl)-1,2,3-triazol-1-yl]-2-oxidanyl-propyl]sulfanyl-6-(hydroxymethyl)oxane-3,5-diol'>J1E</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=6qge FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qge OCA], [~~http~~://pdbe.org/6qge PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6qge RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6qge PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6qge 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=6qge FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qge OCA], [https://pdbe.org/6qge PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6qge RCSB], [https://www.ebi.ac.uk/pdbsum/6qge PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6qge 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;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 19:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 6qge" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6qge" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Galectin 3D structures\|Galectin 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: Logan~~, D T~~]]	+	[[Category: Large Structures]]
-	[[Category: Manzoni, F]]	+	[[Category: Logan DT]]
-	[[Category: Nilsson~~, U J~~]]	+	[[Category: Manzoni F]]
-	[[Category: Oksanen, E]]	+	[[Category: Nilsson UJ]]
-	[[Category: Verteramo~~, M L]]~~	+	[[Category: Oksanen E]]
-	~~[[Category: Cell signalling drug design conformational entropy]]~~	+	[[Category: Verteramo ML]]
-	~~[[Category: Sugar binding protein~~]]	+

OCA at 09:57, 13 February 2019

OCA — Wed, 13 Feb 2019 09:57:55 GMT

←Older revision		Revision as of 09:57, 13 February 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6qge is ~~ON HOLD~~	+	==Galectin-3C in complex with a pair of enantiomeric ligands: S enantiomer==
		+	<StructureSection load='6qge' size='340' side='right' caption='[[6qge]], [[Resolution\|resolution]] 1.16Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6qge]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QGE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6QGE FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=J1E:(2~{S},3~{R},4~{S},5~{R},6~{R})-4-[4-(3-fluorophenyl)-1,2,3-triazol-1-yl]-2-[(2~{S})-3-[4-(3-fluorophenyl)-1,2,3-triazol-1-yl]-2-oxidanyl-propyl]sulfanyl-6-(hydroxymethyl)oxane-3,5-diol'>J1E</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">LGALS3, MAC2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6qge FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qge OCA], [http://pdbe.org/6qge PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6qge RCSB], [http://www.ebi.ac.uk/pdbsum/6qge PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6qge ProSAT]</span></td></tr>
		+	</table>
		+	== 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>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Understanding the driving forces underlying molecular recognition is of fundamental importance in chemistry and biology. The challenge is to unravel the binding thermodynamics into separate contributions and to interpret these in molecular terms. Entropic contributions to the free energy of binding are particularly difficult to assess in this regard. Here we pinpoint the molecular determinants underlying differences in ligand affinity to the carbohydrate recognition domain of galectin-3, using a combination of isothermal titration calorimetry, X-ray crystallography, NMR relaxation, and molecular dynamics simulations followed by conformational entropy and grid inhomogeneous solvation theory (GIST) analyses. Using a pair of diastereomeric ligands that have essentially identical chemical potential in the unbound state, we reduced the problem of dissecting the thermodynamics to a comparison of the two protein-ligand complexes. While the free energies of binding are nearly equal for the R and S diastereomers, greater differences are observed for the enthalpy and entropy, which consequently exhibit compensatory behavior, DeltaDelta H degrees (R - S) = -5 +/- 1 kJ/mol and - TDeltaDelta S degrees (R - S) = 3 +/- 1 kJ/mol. NMR relaxation experiments and molecular dynamics simulations indicate that the protein in complex with the S-stereoisomer has greater conformational entropy than in the R-complex. GIST calculations reveal additional, but smaller, contributions from solvation entropy, again in favor of the S-complex. Thus, conformational entropy apparently dominates over solvation entropy in dictating the difference in the overall entropy of binding. This case highlights an interplay between conformational entropy and solvation entropy, pointing to both opportunities and challenges in drug design.

-	~~Authors: Manzoni, F~~., Verteramo, ~~M.L.~~, ~~Oksanen~~, E., Nilsson, U.J.~~, Logan, D~~.T.	+	Interplay between Conformational Entropy and Solvation Entropy in Protein-Ligand Binding.,Verteramo ML, Stenstrom O, Ignjatovic MM, Caldararu O, Olsson MA, Manzoni F, Leffler H, Oksanen E, Logan DT, Nilsson UJ, Ryde U, Akke M J Am Chem Soc. 2019 Feb 6;141(5):2012-2026. doi: 10.1021/jacs.8b11099. Epub 2019 , Jan 23. PMID:30618244<ref>PMID:30618244</ref>

-	~~Description: Galectin-3C in complex with~~ a ~~pair~~ of ~~enantiomeric ligands:~~ S ~~enantiomer~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
-	[[Category: Logan, D.T]]	+	<div class="pdbe-citations 6qge" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Logan, D T]]
	[[Category: Manzoni, F]]		[[Category: Manzoni, F]]
-	[[Category: ~~Verteramo~~, ~~M.L~~]]	+	[[Category: Nilsson, U J]]
	[[Category: Oksanen, E]]		[[Category: Oksanen, E]]
-	[[Category: ~~Nilsson~~, ~~U.J~~]]	+	[[Category: Verteramo, M L]]
		+	[[Category: Cell signalling drug design conformational entropy]]
		+	[[Category: Sugar binding protein]]

OCA: Protected "6qge" [edit=sysop:move=sysop]

OCA — Wed, 16 Jan 2019 10:54:25 GMT

Protected "6qge" [edit=sysop:move=sysop]

←Older revision

Revision as of 10:54, 16 January 2019

OCA: New page: '''Unreleased structure''' The entry 6qge is ON HOLD Authors: Manzoni, F., Verteramo, M.L., Oksanen, E., Nilsson, U.J., Logan, D.T. Description: Galectin-3C in complex with a pair of e...

OCA — Wed, 16 Jan 2019 10:54:24 GMT

New page: '''Unreleased structure''' The entry 6qge is ON HOLD Authors: Manzoni, F., Verteramo, M.L., Oksanen, E., Nilsson, U.J., Logan, D.T. Description: Galectin-3C in complex with a pair of e...

New page

'''Unreleased structure'''

The entry 6qge is ON HOLD

Authors: Manzoni, F., Verteramo, M.L., Oksanen, E., Nilsson, U.J., Logan, D.T.

Description: Galectin-3C in complex with a pair of enantiomeric ligands: S enantiomer
[[Category: Unreleased Structures]]
[[Category: Logan, D.T]]
[[Category: Manzoni, F]]
[[Category: Verteramo, M.L]]
[[Category: Oksanen, E]]
[[Category: Nilsson, U.J]]