4fk6
From Proteopedia
(Difference between revisions)
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| - | [[ | + | ==JAK1 kinase (JH1 domain) in complex with compound 72== |
| + | <StructureSection load='4fk6' size='340' side='right' caption='[[4fk6]], [[Resolution|resolution]] 2.20Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4fk6]] 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=4FK6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4FK6 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0UJ:N-({1-[(1R,2R,4S)-BICYCLO[2.2.1]HEPT-2-YL]-1,6-DIHYDROIMIDAZO[4,5-D]PYRROLO[2,3-B]PYRIDIN-2-YL}METHYL)METHANESULFONAMIDE'>0UJ</scene></td></tr> | ||
| + | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4e4n|4e4n]], [[4e4l|4e4l]]</td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">JAK1, JAK1A, JAK1B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] </span></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=4fk6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fk6 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4fk6 RCSB], [http://www.ebi.ac.uk/pdbsum/4fk6 PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/JAK1_HUMAN JAK1_HUMAN]] Tyrosine kinase of the non-receptor type, involved in the IFN-alpha/beta/gamma signal pathway. Kinase partner for the interleukin (IL)-2 receptor. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Herein we describe our successful efforts in obtaining C-2 substituted imidazo-pyrrolopyridines with improved JAK1 selectivity relative to JAK2 by targeting an amino acid residue that differs between the two isoforms (JAK1: E966; JAK2: D939). Efforts to improve cellular potency by reducing the polarity of the inhibitors are also detailed. The X-ray crystal structure of a representative inhibitor in complex with the JAK1 enzyme is also disclosed. | ||
| - | + | Structure-based discovery of C-2 substituted imidazo-pyrrolopyridine JAK1 inhibitors with improved selectivity over JAK2.,Labadie S, Dragovich PS, Barrett K, Blair WS, Bergeron P, Chang C, Deshmukh G, Eigenbrot C, Ghilardi N, Gibbons P, Hurley CA, Johnson A, Kenny JR, Kohli PB, Kulagowski JJ, Liimatta M, Lupardus PJ, Mendonca R, Murray JM, Pulk R, Shia S, Steffek M, Ubhayakar S, Ultsch M, van Abbema A, Ward S, Zak M Bioorg Med Chem Lett. 2012 Oct 11. pii: S0960-894X(12)01275-9. doi:, 10.1016/j.bmcl.2012.10.008. PMID:23107482<ref>PMID:23107482</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| + | </div> | ||
| - | + | ==See Also== | |
| - | + | *[[Janus kinase|Janus kinase]] | |
| - | == | + | == References == |
| - | [[ | + | <references/> |
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Non-specific protein-tyrosine kinase]] | [[Category: Non-specific protein-tyrosine kinase]] | ||
| - | [[Category: Eigenbrot, C | + | [[Category: Eigenbrot, C]] |
| - | [[Category: Steffek, M | + | [[Category: Steffek, M]] |
[[Category: Phospho transfer]] | [[Category: Phospho transfer]] | ||
[[Category: Phospho tyrosine]] | [[Category: Phospho tyrosine]] | ||
[[Category: Protein kinase]] | [[Category: Protein kinase]] | ||
[[Category: Transferase-transferase inhibitor complex]] | [[Category: Transferase-transferase inhibitor complex]] | ||
Revision as of 21:26, 25 December 2014
JAK1 kinase (JH1 domain) in complex with compound 72
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