Proteopedia

4ni7: Difference between revisions

← Older editNewer edit →
No edit summary
No edit summary
Line 1: Line 1:
{{STRUCTURE_4ni7|  PDB=4ni7  |  SCENE=  }}
==Crystal structure of human interleukin 6 in complex with a modified nucleotide aptamer (SOMAMER SL1025)==
===Crystal structure of human interleukin 6 in complex with a modified nucleotide aptamer (SOMAMER SL1025)===
<StructureSection load='4ni7' size='340' side='right' caption='[[4ni7]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
{{ABSTRACT_PUBMED_24415767}}
== Structural highlights ==
 
<table><tr><td colspan='2'>[[4ni7]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NI7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4NI7 FirstGlance]. <br>
==Disease==
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><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=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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IL6, IFNB2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4ni7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ni7 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ni7 RCSB], [http://www.ebi.ac.uk/pdbsum/4ni7 PDBsum]</span></td></tr>
</table>
== Disease ==
[[http://www.uniprot.org/uniprot/IL6_HUMAN IL6_HUMAN]] Genetic variations in IL6 are associated with susceptibility to rheumatoid arthritis systemic juvenile (RASJ) [MIM:[http://omim.org/entry/604302 604302]]. An inflammatory articular disorder with systemic-onset beginning before the age of 16. It represents a subgroup of juvenile arthritis associated with severe extraarticular features and occasionally fatal complications. During active phases of the disorder, patients display a typical daily spiking fever, an evanescent macular rash, lymphadenopathy, hepatosplenomegaly, serositis, myalgia and arthritis.  Note=A IL6 promoter polymorphism is associated with a lifetime risk of development of Kaposi sarcoma in HIV-infected men.  
[[http://www.uniprot.org/uniprot/IL6_HUMAN IL6_HUMAN]] Genetic variations in IL6 are associated with susceptibility to rheumatoid arthritis systemic juvenile (RASJ) [MIM:[http://omim.org/entry/604302 604302]]. An inflammatory articular disorder with systemic-onset beginning before the age of 16. It represents a subgroup of juvenile arthritis associated with severe extraarticular features and occasionally fatal complications. During active phases of the disorder, patients display a typical daily spiking fever, an evanescent macular rash, lymphadenopathy, hepatosplenomegaly, serositis, myalgia and arthritis.  Note=A IL6 promoter polymorphism is associated with a lifetime risk of development of Kaposi sarcoma in HIV-infected men.  
== Function ==
[[http://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.


==Function==
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>
[[http://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.  


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[4ni7]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NI7 OCA].
</div>


==See Also==
==See Also==
*[[Interleukin|Interleukin]]
*[[Interleukin|Interleukin]]
 
== References ==
==Reference==
<references/>
<ref group="xtra">PMID:024415767</ref><references group="xtra"/><references/>
__TOC__
[[Category: Clifton, M.]]
</StructureSection>
[[Category: Davies, D.]]
[[Category: Human]]
[[Category: Edwards, T.]]
[[Category: Clifton, M]]
[[Category: Gelinas, A.]]
[[Category: Davies, D]]
[[Category: Jarvis, T.]]
[[Category: Edwards, T]]
[[Category: Gelinas, A]]
[[Category: Jarvis, T]]
[[Category: Cytokine-dna complex]]
[[Category: Cytokine-dna complex]]
[[Category: Interleukin-6]]
[[Category: Interleukin-6]]

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA
Retrieved from "https://proteopedia.openfox.io/w/4ni7"