|
|
| Line 3: |
Line 3: |
| | <StructureSection load='6gps' size='340' side='right'caption='[[6gps]], [[Resolution|resolution]] 3.30Å' scene=''> | | <StructureSection load='6gps' size='340' side='right'caption='[[6gps]], [[Resolution|resolution]] 3.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6gps]] is a 1 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=6GPS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GPS FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6gps]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Clostridium_pasteurianum Clostridium pasteurianum] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GPS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6GPS 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=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.3Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5t1a|5t1a]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=ZN:ZINC+ION'>ZN</scene></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'>[https://proteopedia.org/fgij/fg.htm?mol=6gps FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gps OCA], [https://pdbe.org/6gps PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6gps RCSB], [https://www.ebi.ac.uk/pdbsum/6gps PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6gps 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=6gps FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gps OCA], [http://pdbe.org/6gps PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gps RCSB], [http://www.ebi.ac.uk/pdbsum/6gps PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gps ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == 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> | + | [https://www.uniprot.org/uniprot/RUBR_CLOPA RUBR_CLOPA] Rubredoxin is a small nonheme, iron protein lacking acid-labile sulfide. Its single Fe, chelated to 4 Cys, functions as an electron acceptor and may also stabilize the conformation of the molecule.[https://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> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 24: |
Line 23: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Clostridium pasteurianum]] |
| | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Pautsch, A]] | + | [[Category: Pautsch A]] |
| - | [[Category: Schnapp, G]] | + | [[Category: Schnapp G]] |
| - | [[Category: Drug-design]]
| + | |
| - | [[Category: Gpcr]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| - | [[Category: Signalling]]
| + | |
| Structural highlights
Function
RUBR_CLOPA Rubredoxin is a small nonheme, iron protein lacking acid-labile sulfide. Its single Fe, chelated to 4 Cys, functions as an electron acceptor and may also stabilize the conformation of the molecule.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.[1]
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[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Tan JH, Ludeman JP, Wedderburn J, Canals M, Hall P, Butler SJ, Taleski D, Christopoulos A, Hickey MJ, Payne RJ, Stone MJ. Tyrosine sulfation of chemokine receptor CCR2 enhances interactions with both monomeric and dimeric forms of the chemokine monocyte chemoattractant protein-1 (MCP-1). J Biol Chem. 2013 Apr 5;288(14):10024-34. doi: 10.1074/jbc.M112.447359. Epub 2013, Feb 13. PMID:23408426 doi:http://dx.doi.org/10.1074/jbc.M112.447359
- ↑ Apel AK, Cheng RKY, Tautermann CS, Brauchle M, Huang CY, Pautsch A, Hennig M, Nar H, Schnapp G. Crystal Structure of CC Chemokine Receptor 2A in Complex with an Orthosteric Antagonist Provides Insights for the Design of Selective Antagonists. Structure. 2018 Nov 12. pii: S0969-2126(18)30388-5. doi:, 10.1016/j.str.2018.10.027. PMID:30581043 doi:http://dx.doi.org/10.1016/j.str.2018.10.027
|
