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| | ==JAK1 kinase (JH1 domain) in complex with compound 6== | | ==JAK1 kinase (JH1 domain) in complex with compound 6== |
| - | <StructureSection load='4k77' size='340' side='right' caption='[[4k77]], [[Resolution|resolution]] 2.40Å' scene=''> | + | <StructureSection load='4k77' size='340' side='right'caption='[[4k77]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4k77]] 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=4K77 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4K77 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4k77]] 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=4K77 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4K77 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1Q4:4-(CYCLOHEXYLAMINO)PYRIDO[3,4-D]PYRIMIDIN-8(7H)-ONE'>1Q4</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]] 2.4Å</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1Q4:4-(CYCLOHEXYLAMINO)PYRIDO[3,4-D]PYRIMIDIN-8(7H)-ONE'>1Q4</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></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 HUMAN])</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=4k77 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k77 OCA], [https://pdbe.org/4k77 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4k77 RCSB], [https://www.ebi.ac.uk/pdbsum/4k77 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4k77 ProSAT]</span></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=4k77 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k77 OCA], [http://pdbe.org/4k77 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4k77 RCSB], [http://www.ebi.ac.uk/pdbsum/4k77 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4k77 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == 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. | + | [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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[Janus kinase|Janus kinase]] | + | *[[Janus kinase 3D structures|Janus kinase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Non-specific protein-tyrosine kinase]] | + | [[Category: Large Structures]] |
| - | [[Category: Eigenbrot, C]] | + | [[Category: Eigenbrot C]] |
| - | [[Category: Shia, S]] | + | [[Category: Shia S]] |
| - | [[Category: Phosphotransfer]]
| + | |
| - | [[Category: Protein kinase]]
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| - | [[Category: Transferase-transferase inhibitor complex]]
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| Structural highlights
Function
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.
Publication Abstract from PubMed
A highly ligand efficient, novel 8-oxo-pyridopyrimidine containing inhibitor of Jak1 and Jak2 isoforms with a pyridone moiety as the hinge-binding motif was discovered. Structure-based design strategies were applied to significantly improve enzyme potency and the polarity of the molecule was adjusted to gain cellular activity. The crystal structures of two representative inhibitors bound to Jak1 were obtained to enable SAR exploration.
Design and evaluation of novel 8-oxo-pyridopyrimidine Jak1/2 inhibitors.,Labadie S, Barrett K, Blair WS, Chang C, Deshmukh G, Eigenbrot C, Gibbons P, Johnson A, Kenny JR, Kohli PB, Liimatta M, Lupardus PJ, Shia S, Steffek M, Ubhayakar S, Abbema AV, Zak M Bioorg Med Chem Lett. 2013 Aug 27. pii: S0960-894X(13)01022-6. doi:, 10.1016/j.bmcl.2013.08.082. PMID:24042009[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Labadie S, Barrett K, Blair WS, Chang C, Deshmukh G, Eigenbrot C, Gibbons P, Johnson A, Kenny JR, Kohli PB, Liimatta M, Lupardus PJ, Shia S, Steffek M, Ubhayakar S, Abbema AV, Zak M. Design and evaluation of novel 8-oxo-pyridopyrimidine Jak1/2 inhibitors. Bioorg Med Chem Lett. 2013 Aug 27. pii: S0960-894X(13)01022-6. doi:, 10.1016/j.bmcl.2013.08.082. PMID:24042009 doi:10.1016/j.bmcl.2013.08.082
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