4r8i
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==High Resolution Structure of a Mirror-Image RNA Oligonucleotide Aptamer in Complex with the Chemokine CCL2== | |
| + | <StructureSection load='4r8i' size='340' side='right'caption='[[4r8i]], [[Resolution|resolution]] 2.05Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4r8i]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4R8I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4R8I FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.05Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0A:L-ADENOSINE-5-MONOPHOSPHATE'>0A</scene>, <scene name='pdbligand=0C:L-CYTIDINE-5-MONOPHOSPHATE'>0C</scene>, <scene name='pdbligand=0G:L-GUANOSINE-5-MONOPHOSPHATE'>0G</scene>, <scene name='pdbligand=0U:L-URIDINE-5-MONOPHOSPHATE'>0U</scene>, <scene name='pdbligand=0U1:2-METHYLSELENYL-2-DEOXY-L-URIDINE-5-MONOPHOSPHATE'>0U1</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=SR:STRONTIUM+ION'>SR</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=4r8i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r8i OCA], [https://pdbe.org/4r8i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4r8i RCSB], [https://www.ebi.ac.uk/pdbsum/4r8i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4r8i ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == 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;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | We report the crystal structure of a 40mer mirror-image RNA oligonucleotide completely built from nucleotides of the non-natural L-chirality in complex with the pro-inflammatory chemokine L-CLL2 (monocyte chemoattractant protein-1), a natural protein composed of regular L-amino acids. The L-oligonucleotide is an L-aptamer (a Spiegelmer) identified to bind L-CCL2 with high affinity, thereby neutralizing the chemokine's activity. CCL2 plays a key role in attracting and positioning monocytes; its overexpression in several inflammatory diseases makes CCL2 an interesting pharmacological target. The PEGylated form of the L-aptamer, NOX-E36 (emapticap pegol), already showed promising efficacy in clinical Phase II studies conducted in diabetic nephropathy patients. The structure of the L-oligonucleotide.L-protein complex was solved and refined to 2.05 A. It unveils the L-aptamer's intramolecular contacts and permits a detailed analysis of its structure-function relationship. Furthermore, the analysis of the intermolecular drug-target interactions reveals insight into the selectivity of the L-aptamer for certain related chemokines. | ||
| - | + | Crystal structure of a mirror-image L-RNA aptamer (Spiegelmer) in complex with the natural L-protein target CCL2.,Oberthur D, Achenbach J, Gabdulkhakov A, Buchner K, Maasch C, Falke S, Rehders D, Klussmann S, Betzel C Nat Commun. 2015 Apr 22;6:6923. doi: 10.1038/ncomms7923. PMID:25901662<ref>PMID:25901662</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| + | </div> | ||
| + | <div class="pdbe-citations 4r8i" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Monocyte chemoattractant protein|Monocyte chemoattractant protein]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Synthetic construct]] | ||
| + | [[Category: Achenbach J]] | ||
| + | [[Category: Betzel C]] | ||
| + | [[Category: Buchner K]] | ||
| + | [[Category: Falke S]] | ||
| + | [[Category: Gabdulkhakov A]] | ||
| + | [[Category: Klussmann S]] | ||
| + | [[Category: Maasch C]] | ||
| + | [[Category: Oberthuer D]] | ||
| + | [[Category: Rehders D]] | ||
Current revision
High Resolution Structure of a Mirror-Image RNA Oligonucleotide Aptamer in Complex with the Chemokine CCL2
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