4c16 | pdb_00004c16

E-selectin lectin, EGF-like and two SCR domains complexed with glycomimetic antagonist

spinqualitylabelsall models 4c16, resolution 1.93Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4c16 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.93Å Ligands: 4WC, CA, FUC, GAL, NAG, Q6Z Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Selectin

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