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4fk6
From Proteopedia
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4fk6]] 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=4FK6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FK6 FirstGlance]. <br> | <table><tr><td colspan='2'>[[4fk6]] 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=4FK6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FK6 FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</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]] 2.2Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</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=4fk6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fk6 OCA], [https://pdbe.org/4fk6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4fk6 RCSB], [https://www.ebi.ac.uk/pdbsum/4fk6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4fk6 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=4fk6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fk6 OCA], [https://pdbe.org/4fk6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4fk6 RCSB], [https://www.ebi.ac.uk/pdbsum/4fk6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4fk6 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[https://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. | [https://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. | ||
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| - | 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> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 4fk6" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
*[[Janus kinase 3D structures|Janus kinase 3D structures]] | *[[Janus kinase 3D structures|Janus kinase 3D structures]] | ||
| - | == References == | ||
| - | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Current revision
JAK1 kinase (JH1 domain) in complex with compound 72
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