4c8b
From Proteopedia
(Difference between revisions)
| Line 1: | Line 1: | ||
| - | + | ==Structure of the kinase domain of human RIPK2 in complex with ponatinib== | |
| - | + | <StructureSection load='4c8b' size='340' side='right' caption='[[4c8b]], [[Resolution|resolution]] 2.75Å' scene=''> | |
| - | + | == Structural highlights == | |
| - | ==Function== | + | <table><tr><td colspan='2'>[[4c8b]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4C8B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4C8B FirstGlance]. <br> |
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0LI:3-(IMIDAZO[1,2-B]PYRIDAZIN-3-YLETHYNYL)-4-METHYL-N-{4-[(4-METHYLPIPERAZIN-1-YL)METHYL]-3-(TRIFLUOROMETHYL)PHENYL}BENZAMIDE'>0LI</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></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=4c8b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4c8b OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4c8b RCSB], [http://www.ebi.ac.uk/pdbsum/4c8b PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
[[http://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> | [[http://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> | ||
| - | + | == References == | |
| - | == | + | <references/> |
| - | + | __TOC__ | |
| - | + | </StructureSection> | |
| - | + | ||
| - | <references | + | |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
| - | [[Category: Arrowsmith, C H | + | [[Category: Arrowsmith, C H]] |
| - | [[Category: Bountra, C | + | [[Category: Bountra, C]] |
| - | [[Category: Bradley, A | + | [[Category: Bradley, A]] |
| - | [[Category: Bullock, A | + | [[Category: Bullock, A]] |
| - | [[Category: Canning, P | + | [[Category: Canning, P]] |
| - | [[Category: Delft, F von | + | [[Category: Delft, F von]] |
| - | [[Category: Edwards, A M | + | [[Category: Edwards, A M]] |
| - | [[Category: Goubin, S | + | [[Category: Goubin, S]] |
| - | [[Category: Krojer, T | + | [[Category: Krojer, T]] |
| - | [[Category: Mahajan, P | + | [[Category: Mahajan, P]] |
[[Category: Structural genomic]] | [[Category: Structural genomic]] | ||
[[Category: Transferase]] | [[Category: Transferase]] | ||
Revision as of 07:17, 25 December 2014
Structure of the kinase domain of human RIPK2 in complex with ponatinib
| |||||||||||
