4uai: Difference between revisions
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<StructureSection load='4uai' size='340' side='right' caption='[[4uai]], [[Resolution|resolution]] 1.90Å' scene=''> | <StructureSection load='4uai' size='340' side='right' caption='[[4uai]], [[Resolution|resolution]] 1.90Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4uai]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4UAI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4UAI FirstGlance]. <br> | <table><tr><td colspan='2'>[[4uai]] is a 2 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=4UAI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4UAI FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3GG:1-PHENYL-3-[4-(1H-TETRAZOL-5-YL)PHENYL]UREA'>3GG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3GG:1-PHENYL-3-[4-(1H-TETRAZOL-5-YL)PHENYL]UREA'>3GG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CXCL12, SDF1, SDF1A, SDF1B ([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=4uai FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4uai OCA], [http://pdbe.org/4uai PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4uai RCSB], [http://www.ebi.ac.uk/pdbsum/4uai PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4uai ProSAT]</span></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=4uai FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4uai OCA], [http://pdbe.org/4uai PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4uai RCSB], [http://www.ebi.ac.uk/pdbsum/4uai PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4uai ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human]] | |||
[[Category: Chen, Y]] | [[Category: Chen, Y]] | ||
[[Category: Smith, E W]] | [[Category: Smith, E W]] | ||
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[[Category: Complex]] | [[Category: Complex]] | ||
[[Category: Cxcl12]] | [[Category: Cxcl12]] | ||
[[Category: Cytokine-cytokine inhibitor complex]] | |||
[[Category: Inhibitor]] | [[Category: Inhibitor]] | ||
Revision as of 15:08, 6 November 2017
Crystal structure of CXCL12 in complex with inhibitorCrystal structure of CXCL12 in complex with inhibitor
Structural highlights
Function[SDF1_HUMAN] Chemoattractant active on T-lymphocytes, monocytes, but not neutrophils. Activates the C-X-C chemokine receptor CXCR4 to induce a rapid and transient rise in the level of intracellular calcium ions and chemotaxis. Also binds to another C-X-C chemokine receptor CXCR7, which activates the beta-arrestin pathway and acts as a scavenger receptor for SDF-1. SDF-1-beta(3-72) and SDF-1-alpha(3-67) show a reduced chemotactic activity. Binding to cell surface proteoglycans seems to inhibit formation of SDF-1-alpha(3-67) and thus to preserve activity on local sites. Acts as a positive regulator of monocyte migration and a negative regulator of monocyte adhesion via the LYN kinase. Stimulates migration of monocytes and T-lymphocytes through its receptors, CXCR4 and CXCR7, and decreases monocyte adherence to surfaces coated with ICAM-1, a ligand for beta-2 integrins. SDF1A/CXCR4 signaling axis inhibits beta-2 integrin LFA-1 mediated adhesion of monocytes to ICAM-1 through LYN kinase. Inhibits CXCR4-mediated infection by T-cell line-adapted HIV-1. Plays a protective role after myocardial infarction. Induces down-regulation and internalization of CXCR7 expressed in various cells. Has several critical functions during embryonic development; required for B-cell lymphopoiesis, myelopoiesis in bone marrow and heart ventricular septum formation.[1] [2] [3] [4] [5] [6] Publication Abstract from PubMedCXCL12 binds to CXCR4, promoting both chemotaxis of lymphocytes and metastasis of cancer cells. We previously identified small molecule ligands that bind CXCL12 and block CXCR4-mediated chemotaxis. We now report a 1.9 Angstrom resolution X-ray structure of CXCL12 bound by such a molecule at a site normally bound by sY21 of CXCR4. The complex structure reveals binding hot spots for future inhibitor design and suggests a new approach to targeting CXCL12-CXCR4 signaling in drug discovery. Structural analysis of a novel small molecule ligand bound to the CXCL12 chemokine.,Smith E, Liu Y, Getschman AE, Peterson F, Ziarek JJ, Li R, Volkman BF, Chen Y J Med Chem. 2014 Oct 30. PMID:25356720[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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