View source for 6gpx


==CRYSTAL STRUCTURE OF CCR2A IN COMPLEX WITH MK-0812==
<StructureSection load='6gpx' size='340' side='right'caption='[[6gpx]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6gpx]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_pasteurianus"_(winogradsky_1895)_lehmann_and_neumann_1907 "bacillus pasteurianus" (winogradsky 1895) lehmann and neumann 1907]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GPX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GPX FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=F7N:[(3~{S},4~{S})-3-methoxyoxan-4-yl]-[(1~{R},3~{S})-3-propan-2-yl-3-[[3-(trifluoromethyl)-7,8-dihydro-5~{H}-1,6-naphthyridin-6-yl]carbonyl]cyclopentyl]azanium'>F7N</scene>, <scene name='pdbligand=OLA:OLEIC+ACID'>OLA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5t1a|5t1a]], [[6gps|6gps]]</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CCR2, CMKBR2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1501 "Bacillus pasteurianus" (Winogradsky 1895) Lehmann and Neumann 1907])</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=6gpx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gpx OCA], [http://pdbe.org/6gpx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gpx RCSB], [http://www.ebi.ac.uk/pdbsum/6gpx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gpx ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/CCR2_HUMAN CCR2_HUMAN]] Receptor for the CCL2, CCL7 and CCL13 chemokines. Transduces a signal by increasing intracellular calcium ion levels. Alternative coreceptor with CD4 for HIV-1 infection.<ref>PMID:23408426</ref>  
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== Publication Abstract from PubMed ==
We determined two crystal structures of the chemokine receptor CCR2A in complex with the orthosteric antagonist MK-0812. Full-length CCR2A, stabilized by rubredoxin and a series of five mutations were resolved at 3.3 A. An N- and C-terminally truncated CCR2A construct was crystallized in an alternate crystal form, which yielded a 2.7 A resolution structure using serial synchrotron crystallography. Our structures provide a clear structural explanation for the observed key role of residue E291(7.39) in high-affinity binding of several orthosteric CCR2 antagonists. By combining all the structural information collected, we generated models of co-structures for the structurally diverse pyrimidine amide class of CCR2 antagonists. Even though the representative Ex15 overlays well with MK-0812, it also interacts with the non-conserved H121(3.33), resulting in a significant selectivity over CCR5. Insights derived from this work will facilitate drug discovery efforts directed toward highly selective CCR2 antagonists with potentially superior efficacy.

Crystal Structure of CC Chemokine Receptor 2A in Complex with an Orthosteric Antagonist Provides Insights for the Design of Selective Antagonists.,Apel AK, Cheng RKY, Tautermann CS, Brauchle M, Huang CY, Pautsch A, Hennig M, Nar H, Schnapp G Structure. 2018 Nov 12. pii: S0969-2126(18)30388-5. doi:, 10.1016/j.str.2018.10.027. PMID:30581043<ref>PMID:30581043</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6gpx" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Apel, A]]
[[Category: Cheng, R]]
[[Category: Pautsch, A]]
[[Category: Schnapp, G]]
[[Category: Drug-design]]
[[Category: Gpcr]]
[[Category: Signaling protein]]
[[Category: Signalling]]