4r8i

From Proteopedia

(Difference between revisions)

Current revision

High Resolution Structure of a Mirror-Image RNA Oligonucleotide Aptamer in Complex with the Chemokine CCL2

Structural highlights

4r8i is a 2 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.05Å
Ligands:	, , , , , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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 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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Oberthur D, Achenbach J, Gabdulkhakov A, Buchner K, Maasch C, Falke S, Rehders D, Klussmann S, Betzel C. Crystal structure of a mirror-image L-RNA aptamer (Spiegelmer) in complex with the natural L-protein target CCL2. Nat Commun. 2015 Apr 22;6:6923. doi: 10.1038/ncomms7923. PMID:25901662 doi:http://dx.doi.org/10.1038/ncomms7923

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4r8i"

@@ Line 4: / Line 4: @@
 == 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='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>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.05&#8491;</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>

4r8i

From Proteopedia

Current revision

High Resolution Structure of a Mirror-Image RNA Oligonucleotide Aptamer in Complex with the Chemokine CCL2

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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