3oe6: Difference between revisions
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==Crystal structure of the CXCR4 chemokine receptor in complex with a small molecule antagonist IT1t in I222 spacegroup== | |||
<StructureSection load='3oe6' size='340' side='right' caption='[[3oe6]], [[Resolution|resolution]] 3.20Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3oe6]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3OE6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3OE6 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=ITD:(6,6-DIMETHYL-5,6-DIHYDROIMIDAZO[2,1-B][1,3]THIAZOL-3-YL)METHYL+N,N-DICYCLOHEXYLIMIDOTHIOCARBAMATE'>ITD</scene>, <scene name='pdbligand=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3odu|3odu]], [[3oe0|3oe0]], [[3oe8|3oe8]], [[3oe9|3oe9]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CXCR4, CXCR4_HUMAN,E ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Lysozyme Lysozyme], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.17 3.2.1.17] </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=3oe6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3oe6 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3oe6 RCSB], [http://www.ebi.ac.uk/pdbsum/3oe6 PDBsum]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[[http://www.uniprot.org/uniprot/CXCR4_HUMAN CXCR4_HUMAN]] Defects in CXCR4 are a cause of WHIM syndrome (WHIM) [MIM:[http://omim.org/entry/193670 193670]]; also known as warts, hypogammaglobulinemia, infections and myelokathexis. WHIM syndrome is an immunodeficiency disease characterized by neutropenia, hypogammaglobulinemia and extensive human papillomavirus (HPV) infection. Despite the peripheral neutropenia, bone marrow aspirates from affected individuals contain abundant mature myeloid cells, a condition termed myelokathexis.<ref>PMID:12692554</ref> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/CXCR4_HUMAN CXCR4_HUMAN]] Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation. Acts as a receptor for extracellular ubiquitin; leading to enhanced intracellular calcium ions and reduced cellular cAMP levels. Involved in hematopoiesis and in cardiac ventricular septum formation. Also plays an essential role in vascularization of the gastrointestinal tract, probably by regulating vascular branching and/or remodeling processes in endothelial cells. Involved in cerebellar development. In the CNS, could mediate hippocampal-neuron survival. Acts as a coreceptor (CD4 being the primary receptor) for HIV-1 X4 isolates and as a primary receptor for some HIV-2 isolates. Promotes Env-mediated fusion of the virus.<ref>PMID:8329116</ref> <ref>PMID:8234909</ref> <ref>PMID:8629022</ref> <ref>PMID:8752280</ref> <ref>PMID:8752281</ref> <ref>PMID:10074102</ref> <ref>PMID:10644702</ref> <ref>PMID:10825158</ref> <ref>PMID:17197449</ref> <ref>PMID:20048153</ref> <ref>PMID:20228059</ref> <ref>PMID:20505072</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Chemokine receptors are critical regulators of cell migration in the context of immune surveillance, inflammation, and development. The G protein-coupled chemokine receptor, CXCR4, is specifically implicated in cancer metastasis and HIV-1 infection. Here, we report five independent crystal structures of CXCR4 bound to an antagonist small molecule IT1t and a cyclic peptide CVX15 at 2.5 to 3.2 angstrom resolution. All structures reveal a consistent homodimer with an interface including helices V and VI that may be involved in regulating signaling. The location and shape of the ligand-binding sites differ from other G protein-coupled receptors (GPCRs) and are closer to the extracellular surface. These structures provide new clues about the interactions between CXCR4 and its natural ligand CXCL12 and with the HIV-1 glycoprotein gp120. | |||
Structures of the CXCR4 Chemokine GPCR with Small-Molecule and Cyclic Peptide Antagonists.,Wu B, Chien EY, Mol CD, Fenalti G, Liu W, Katritch V, Abagyan R, Brooun A, Wells P, Bi FC, Hamel DJ, Kuhn P, Handel TM, Cherezov V, Stevens RC Science. 2010 Oct 7. PMID:20929726<ref>PMID:20929726</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | ==See Also== | ||
*[[CXC chemokine receptor type 4|CXC chemokine receptor type 4]] | *[[CXC chemokine receptor type 4|CXC chemokine receptor type 4]] | ||
*[[ | *[[Lysozyme 3D structures|Lysozyme 3D structures]] | ||
== References == | |||
<references/> | |||
== | __TOC__ | ||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Lysozyme]] | [[Category: Lysozyme]] | ||
[[Category: ATCG3D, Accelerated Technologies Center for Gene to 3D Structure | [[Category: ATCG3D, Accelerated Technologies Center for Gene to 3D Structure]] | ||
[[Category: Cherezov, V | [[Category: Cherezov, V]] | ||
[[Category: Chien, E Y.T | [[Category: Chien, E Y.T]] | ||
[[Category: GPCR, GPCR Network | [[Category: GPCR, GPCR Network]] | ||
[[Category: Han, G W | [[Category: Han, G W]] | ||
[[Category: Katritch, V | [[Category: Katritch, V]] | ||
[[Category: Liu, W | [[Category: Liu, W]] | ||
[[Category: Mol, C D | [[Category: Mol, C D]] | ||
[[Category: Stevens, R C | [[Category: Stevens, R C]] | ||
[[Category: Wu, B | [[Category: Wu, B]] | ||
[[Category: Accelerated technologies center for gene to 3d structure]] | [[Category: Accelerated technologies center for gene to 3d structure]] | ||
[[Category: Atcg3d]] | [[Category: Atcg3d]] | ||
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[[Category: It1t]] | [[Category: It1t]] | ||
[[Category: Membrane protein]] | [[Category: Membrane protein]] | ||
[[Category: Protein structure initiative | [[Category: PSI, Protein structure initiative]] | ||
[[Category: Psi-biology]] | [[Category: Psi-biology]] | ||
[[Category: Sdf1]] | [[Category: Sdf1]] | ||