4dn4: Difference between revisions
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==Crystal structure of the complex between cnto888 fab and mcp-1 mutant p8a== | ==Crystal structure of the complex between cnto888 fab and mcp-1 mutant p8a== | ||
<StructureSection load='4dn4' size='340' side='right' caption='[[4dn4]], [[Resolution|resolution]] 2.80Å' scene=''> | <StructureSection load='4dn4' size='340' side='right'caption='[[4dn4]], [[Resolution|resolution]] 2.80Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4dn4]] is a 3 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4dn4]] is a 3 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=4DN4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DN4 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=4dn4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dn4 OCA], [https://pdbe.org/4dn4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dn4 RCSB], [https://www.ebi.ac.uk/pdbsum/4dn4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dn4 ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[[ | [[https://www.uniprot.org/uniprot/CCL2_HUMAN CCL2_HUMAN]] Chemotactic factor that attracts monocytes and basophils but not neutrophils or eosinophils. Augments monocyte anti-tumor activity. Has been implicated in the pathogenesis of diseases characterized by monocytic infiltrates, like psoriasis, rheumatoid arthritis or atherosclerosis. May be involved in the recruitment of monocytes into the arterial wall during the disease process of atherosclerosis. | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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==See Also== | ==See Also== | ||
*[[ | *[[Monocyte chemoattractant protein|Monocyte chemoattractant protein]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Gilliland | [[Category: Large Structures]] | ||
[[Category: Grygiel | [[Category: Gilliland G]] | ||
[[Category: Malia | [[Category: Grygiel T]] | ||
[[Category: Obmolova | [[Category: Malia T]] | ||
[[Category: Snyder | [[Category: Obmolova G]] | ||
[[Category: Sweet | [[Category: Snyder L]] | ||
[[Category: Teplyakov | [[Category: Sweet R]] | ||
[[Category: Teplyakov A]] | |||
Revision as of 11:29, 21 September 2022
Crystal structure of the complex between cnto888 fab and mcp-1 mutant p8aCrystal structure of the complex between cnto888 fab and mcp-1 mutant p8a
Structural highlights
Function[CCL2_HUMAN] Chemotactic factor that attracts monocytes and basophils but not neutrophils or eosinophils. Augments monocyte anti-tumor activity. Has been implicated in the pathogenesis of diseases characterized by monocytic infiltrates, like psoriasis, rheumatoid arthritis or atherosclerosis. May be involved in the recruitment of monocytes into the arterial wall during the disease process of atherosclerosis. Publication Abstract from PubMedHuman CC chemokine ligand 2 (CCL2), also known as monocyte chemoattractant protein-1 (MCP-1), is a member of the beta chemokine family whose actions are mediated through the G-protein-coupled receptor CCR2. Binding of CCL2 to its receptor CCR2 triggers calcium mobilization and chemotaxis. CCL2 is implicated in the pathogenesis of certain inflammatory diseases and cancer. CNTO 888, a neutralizing human anti-CCL2 antibody, was derived by antibody phage display. The antibody binds human CCL2 with high affinity (K(D)=22 pM) and inhibits CCL2 binding to its receptor. The crystal structure of the CNTO 888 Fab alone and in complex with the monomeric form of CCL2 (P8A variant) was determined at 2.6 A and 2.8 A resolution, respectively. CNTO 888 recognizes a conformational epitope encompassing residues 18-24 and 45-51 that overlaps the mapped receptor binding site. The epitope of CNTO 888 does not overlap with the dimerization site of CCL2, and thus its inhibitory activity is not expected to result from interference with the oligomeric state of CCL2. Comparison of the X-ray-determined epitopes of CNTO 888 and another CCL2-neutralizing antibody, 11K2, provides insight into the molecular basis of antibody selectivity and functional inhibition. Structural basis for high selectivity of anti-CCL2 neutralizing antibody CNTO 888.,Obmolova G, Teplyakov A, Malia TJ, Grygiel TL, Sweet R, Snyder LA, Gilliland GL Mol Immunol. 2012 Jun;51(2):227-33. Epub 2012 Apr 7. PMID:22487721[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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