4ni9: Difference between revisions

From Proteopedia
Jump to navigationJump to search
← Older editNewer edit →
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,332,807 edits
No edit summary
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,332,807 edits
No edit summary
Line 4: Line 4:
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4ni9]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NI9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NI9 FirstGlance]. <br>
<table><tr><td colspan='2'>[[4ni9]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NI9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NI9 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2JU:2-DEOXY-5-[(NAPHTHALEN-1-YLMETHYL)CARBAMOYL]URIDINE+5-(DIHYDROGEN+PHOSPHATE)'>2JU</scene>, <scene name='pdbligand=A2M:2-O-METHYLADENOSINE+5-(DIHYDROGEN+PHOSPHATE)'>A2M</scene>, <scene name='pdbligand=DUZ:5-(BENZYLCARBAMOYL)-2-DEOXYURIDINE+5-(DIHYDROGEN+PHOSPHATE)'>DUZ</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=OMC:O2-METHYLYCYTIDINE-5-MONOPHOSPHATE'>OMC</scene>, <scene name='pdbligand=OMG:O2-METHYLGUANOSINE-5-MONOPHOSPHATE'>OMG</scene>, <scene name='pdbligand=UPE:2-DEOXY-5-[(2-PHENYLETHYL)CARBAMOYL]URIDINE+5-(DIHYDROGEN+PHOSPHATE)'>UPE</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]] 2.55&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2JU:2-DEOXY-5-[(NAPHTHALEN-1-YLMETHYL)CARBAMOYL]URIDINE+5-(DIHYDROGEN+PHOSPHATE)'>2JU</scene>, <scene name='pdbligand=A2M:2-O-METHYLADENOSINE+5-(DIHYDROGEN+PHOSPHATE)'>A2M</scene>, <scene name='pdbligand=DUZ:5-(BENZYLCARBAMOYL)-2-DEOXYURIDINE+5-(DIHYDROGEN+PHOSPHATE)'>DUZ</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=OMC:O2-METHYLYCYTIDINE-5-MONOPHOSPHATE'>OMC</scene>, <scene name='pdbligand=OMG:O2-METHYLGUANOSINE-5-MONOPHOSPHATE'>OMG</scene>, <scene name='pdbligand=UPE:2-DEOXY-5-[(2-PHENYLETHYL)CARBAMOYL]URIDINE+5-(DIHYDROGEN+PHOSPHATE)'>UPE</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=4ni9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ni9 OCA], [https://pdbe.org/4ni9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ni9 RCSB], [https://www.ebi.ac.uk/pdbsum/4ni9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ni9 ProSAT]</span></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=4ni9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ni9 OCA], [https://pdbe.org/4ni9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ni9 RCSB], [https://www.ebi.ac.uk/pdbsum/4ni9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ni9 ProSAT]</span></td></tr>
</table>
</table>
Line 11: Line 12:
== Function ==
== Function ==
[https://www.uniprot.org/uniprot/IL6_HUMAN IL6_HUMAN] Cytokine with a wide variety of biological functions. It is a potent inducer of the acute phase response. Plays an essential role in the final differentiation of B-cells into Ig-secreting cells Involved in lymphocyte and monocyte differentiation. It induces myeloma and plasmacytoma growth and induces nerve cells differentiation Acts on B-cells, T-cells, hepatocytes, hematopoietic progenitor cells and cells of the CNS. Also acts as a myokine. It is discharged into the bloodstream after muscle contraction and acts to increase the breakdown of fats and to improve insulin resistance.
[https://www.uniprot.org/uniprot/IL6_HUMAN IL6_HUMAN] Cytokine with a wide variety of biological functions. It is a potent inducer of the acute phase response. Plays an essential role in the final differentiation of B-cells into Ig-secreting cells Involved in lymphocyte and monocyte differentiation. It induces myeloma and plasmacytoma growth and induces nerve cells differentiation Acts on B-cells, T-cells, hepatocytes, hematopoietic progenitor cells and cells of the CNS. Also acts as a myokine. It is discharged into the bloodstream after muscle contraction and acts to increase the breakdown of fats and to improve insulin resistance.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
IL-6 is a secreted cytokine that functions through binding two cell surface receptors, IL-6Ralpha and gp130. Due to its involvement in the progression of several chronic inflammatory diseases, IL-6 is a target of pharmacologic interest. We have recently identified a novel class of ligands called SOMAmers (Slow Off-rate Modified Aptamers) that bind IL-6 and inhibit its biological activity. SOMAmers exploit the chemical diversity of protein-like side chains assembled on flexible nucleic acid scaffolds, resulting in an expanded repertoire of intra- and intermolecular interactions not achievable with conventional aptamers. Here we report the co-crystal structure of a high-affinity SOMAmer (Kd=0.20 nM) modified at the 5-position of deoxyuridine in a complex with IL-6. The SOMAmer, comprised of a G-quartet domain and a stem-loop domain, engages IL-6 in a clamp-like manner over an extended surface exhibiting close shape complementarity with the protein. The interface is characterized by substantial hydrophobic interactions overlapping the binding surfaces of the IL-6Ralpha and gp130 receptors. The G-quartet domain retains considerable binding activity as a disconnected autonomous fragment (Kd=270 nM). A single substitution from our diverse modified nucleotide library leads to a 37-fold enhancement in binding affinity of the G-quartet fragment (Kd=7.4 nM). The ability to probe ligand surfaces in this manner is a powerful tool in the development of new therapeutic reagents with improved pharmacologic properties. The SOMAmer:IL-6 structure also expands our understanding of the diverse structural motifs achievable with modified nucleic acid libraries and elucidates the nature with which these unique ligands interact with their protein targets.
Crystal Structure of Interleukin-6 in Complex with a Modified Nucleic Acid Ligand.,Gelinas AD, Davies DR, Edwards TE, Rohloff JC, Carter JD, Zhang C, Gupta S, Ishikawa Y, Hirota M, Nakaishi Y, Jarvis TC, Janjic N J Biol Chem. 2014 Jan 12. PMID:24415767<ref>PMID:24415767</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4ni9" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Interleukin 3D structures|Interleukin 3D structures]]
*[[Interleukin 3D structures|Interleukin 3D structures]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>

Revision as of 06:50, 3 April 2024

Crystal structure of human interleukin 6 in complex with a modified nucleotide aptamer (SOMAMER SL1025), FORM 2

4ni9, resolution 2.55Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "https://proteopedia.org/index.php?title=4ni9&oldid=4119100"