5ng2

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'''Unreleased structure'''
 
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The entry 5ng2 is ON HOLD
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==Structure of RIP2K(D146N) with bound Staurosporine==
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<StructureSection load='5ng2' size='340' side='right'caption='[[5ng2]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[5ng2]] is a 2 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=5NG2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5NG2 FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=STU:STAUROSPORINE'>STU</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5ng2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ng2 OCA], [https://pdbe.org/5ng2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ng2 RCSB], [https://www.ebi.ac.uk/pdbsum/5ng2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ng2 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/RIPK2_HUMAN RIPK2_HUMAN] Serine/threonine/tyrosine kinase that plays an essential role in modulation of innate and adaptive immune responses. Upon stimulation by bacterial peptidoglycans, NOD1 and NOD2 are activated, oligomerize and recruit RIPK2 through CARD-CARD domains. Once recruited, RIPK2 autophosphorylates and undergoes 'Lys-63'-linked polyubiquitination by E3 ubiquitin ligases BIRC2 and BIRC3. The polyubiquitinated protein mediates the recruitment of MAP3K7/TAK1 to IKBKG/NEMO and induces 'Lys-63'-linked polyubiquitination of IKBKG/NEMO and subsequent activation of IKBKB/IKKB. In turn, NF-kappa-B is released from NF-kappa-B inhibitors and translocates into the nucleus where it activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis. Plays also a role during engagement of the T-cell receptor (TCR) in promoting BCL10 phosphorylation and subsequent NF-kappa-B activation.<ref>PMID:14638696</ref> <ref>PMID:17054981</ref> <ref>PMID:18079694</ref> <ref>PMID:21123652</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Innate immune receptors NOD1 and NOD2 are activated by bacterial peptidoglycans leading to recruitment of adaptor kinase RIP2, which, upon phosphorylation and ubiquitination, becomes a scaffold for downstream effectors. The kinase domain (RIP2K) is a pharmaceutical target for inflammatory diseases caused by aberrant NOD2-RIP2 signalling. Although structures of active RIP2K in complex with inhibitors have been reported, the mechanism of RIP2K activation remains to be elucidated. Here we analyse RIP2K activation by combining crystal structures of the active and inactive states with mass spectrometric characterization of their phosphorylation profiles. The active state has Helix alphaC inwardly displaced and the phosphorylated Activation Segment (AS) disordered, whilst in the inactive state Helix alphaC is outwardly displaced and packed against the helical, non-phosphorylated AS. Biophysical measurements show that the active state is a stable dimer whilst the inactive kinase is in a monomer-dimer equilibrium, consistent with the observed structural differences at the dimer interface. We conclude that RIP2 kinase auto-phosphorylation is intimately coupled to dimerization, similar to the case of BRAF. Our results will help drug design efforts targeting RIP2 as a potential treatment for NOD2-RIP2 related inflammatory diseases.
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Authors: Pellegrini, E., Cusack, S.
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Structures of the inactive and active states of RIP2 kinase inform on the mechanism of activation.,Pellegrini E, Signor L, Singh S, Boeri Erba E, Cusack S PLoS One. 2017 May 18;12(5):e0177161. doi: 10.1371/journal.pone.0177161., eCollection 2017. PMID:28545134<ref>PMID:28545134</ref>
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Description: Structure of RIP2K(D146N) with bound Staurosporine
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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[[Category: Cusack, S]]
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<div class="pdbe-citations 5ng2" style="background-color:#fffaf0;"></div>
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[[Category: Pellegrini, E]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Cusack S]]
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[[Category: Pellegrini E]]

Current revision

Structure of RIP2K(D146N) with bound Staurosporine

PDB ID 5ng2

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