4c16: Difference between revisions
New page: '''Unreleased structure''' The entry 4c16 is ON HOLD until sometime in the future Authors: Preston, R.C., Jakob, R.P., Binder, F.P.C., Sager, C.P., Ernst, B., Maier, T. Description: E-... |
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==E-selectin lectin, EGF-like and two SCR domains complexed with glycomimetic antagonist== | |||
<StructureSection load='4c16' size='340' side='right'caption='[[4c16]], [[Resolution|resolution]] 1.93Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4c16]] 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=4C16 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4C16 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]] 1.93Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4WC:(S)-CYCLOHEXYL+LACTIC+ACID'>4WC</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=GAL:BETA-D-GALACTOSE'>GAL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=Q6Z:(1R,2R,3S)-3-METHYLCYCLOHEXANE-1,2-DIOL'>Q6Z</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=4c16 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4c16 OCA], [https://pdbe.org/4c16 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4c16 RCSB], [https://www.ebi.ac.uk/pdbsum/4c16 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4c16 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/LYAM2_HUMAN LYAM2_HUMAN] Cell-surface glycoprotein having a role in immunoadhesion. Mediates in the adhesion of blood neutrophils in cytokine-activated endothelium through interaction with PSGL1/SELPLG. May have a role in capillary morphogenesis.<ref>PMID:1689848</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
E-selectin is a cell-adhesion molecule of the vascular endothelium that promotes essential leukocyte rolling in the early inflammatory response by binding to glycoproteins containing the tetrasaccharide sialyl Lewisx (sLex). Efficient leukocyte recruitment under vascular flow conditions depends on an increased lifetime of E-selectin/ligand complexes under tensile force in a so-called catch-bond binding mode. Co-crystal structures of a representative fragment of the extracellular E-selectin region with sLex and a glycomimetic antagonist thereof reveal an extended E-selectin conformation, which is identified as a high-affinity binding state of E-selectin by molecular dynamics simulations. Small-angle X-ray scattering experiments demonstrate a direct link between ligand binding and E-selectin conformational transition under static conditions in solution. This permits tracing a series of concerted structural changes connecting ligand binding to conformational stretching as the structural basis of E-selectin catch-bond-mediated leukocyte recruitment. The detailed molecular view of the binding site paves the way for the design of a new generation of selectin antagonists. This is of special interest, since their therapeutic potential was recently demonstrated with the pan-selectin antagonists GMI-1070 (Rivipansel). | |||
E-selectin ligand complexes adopt an extended high-affinity conformation.,Preston RC, Jakob RP, Binder FP, Sager CP, Ernst B, Maier T J Mol Cell Biol. 2015 Jun 27. pii: mjv046. PMID:26117840<ref>PMID:26117840</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4c16" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Selectin|Selectin]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Binder FPC]] | |||
[[Category: Ernst B]] | |||
[[Category: Jakob RP]] | |||
[[Category: Maier T]] | |||
[[Category: Preston RC]] | |||
[[Category: Sager CP]] | |||
Latest revision as of 15:01, 20 December 2023
E-selectin lectin, EGF-like and two SCR domains complexed with glycomimetic antagonistE-selectin lectin, EGF-like and two SCR domains complexed with glycomimetic antagonist
Structural highlights
FunctionLYAM2_HUMAN Cell-surface glycoprotein having a role in immunoadhesion. Mediates in the adhesion of blood neutrophils in cytokine-activated endothelium through interaction with PSGL1/SELPLG. May have a role in capillary morphogenesis.[1] Publication Abstract from PubMedE-selectin is a cell-adhesion molecule of the vascular endothelium that promotes essential leukocyte rolling in the early inflammatory response by binding to glycoproteins containing the tetrasaccharide sialyl Lewisx (sLex). Efficient leukocyte recruitment under vascular flow conditions depends on an increased lifetime of E-selectin/ligand complexes under tensile force in a so-called catch-bond binding mode. Co-crystal structures of a representative fragment of the extracellular E-selectin region with sLex and a glycomimetic antagonist thereof reveal an extended E-selectin conformation, which is identified as a high-affinity binding state of E-selectin by molecular dynamics simulations. Small-angle X-ray scattering experiments demonstrate a direct link between ligand binding and E-selectin conformational transition under static conditions in solution. This permits tracing a series of concerted structural changes connecting ligand binding to conformational stretching as the structural basis of E-selectin catch-bond-mediated leukocyte recruitment. The detailed molecular view of the binding site paves the way for the design of a new generation of selectin antagonists. This is of special interest, since their therapeutic potential was recently demonstrated with the pan-selectin antagonists GMI-1070 (Rivipansel). E-selectin ligand complexes adopt an extended high-affinity conformation.,Preston RC, Jakob RP, Binder FP, Sager CP, Ernst B, Maier T J Mol Cell Biol. 2015 Jun 27. pii: mjv046. PMID:26117840[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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