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| | ==Crystal structure of JAK1 in complex with PF-4950736== | | ==Crystal structure of JAK1 in complex with PF-4950736== |
| - | <StructureSection load='5khx' size='340' side='right' caption='[[5khx]], [[Resolution|resolution]] 2.40Å' scene=''> | + | <StructureSection load='5khx' size='340' side='right'caption='[[5khx]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5khx]] is a 1 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=5KHX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5KHX FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5khx]] is a 1 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=5KHX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5KHX FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6TE:~{N}-[3-[METHYL(7~{H}-PYRROLO[2,3-D]PYRIMIDIN-4-YL)AMINO]CYCLOBUTYL]METHANESULFONAMIDE'>6TE</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=6TE:~{N}-[3-[METHYL(7~{H}-PYRROLO[2,3-D]PYRIMIDIN-4-YL)AMINO]CYCLOBUTYL]METHANESULFONAMIDE'>6TE</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=5khx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5khx OCA], [https://pdbe.org/5khx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5khx RCSB], [https://www.ebi.ac.uk/pdbsum/5khx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5khx 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=5khx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5khx OCA], [http://pdbe.org/5khx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5khx RCSB], [http://www.ebi.ac.uk/pdbsum/5khx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5khx 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: Caspers, N L]] | + | [[Category: Caspers NL]] |
| - | [[Category: Han, S]] | + | [[Category: Han S]] |
| - | [[Category: Complex]]
| + | |
| - | [[Category: Inhibitor]]
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| - | [[Category: Jak1]]
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| - | [[Category: Kinase]]
| + | |
| - | [[Category: Transferase-transferase inhibitor complex]]
| + | |
| 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
Crystals of phosphorylated JAK1 kinase domain were initially generated in complex with nucleotide (ADP) and magnesium. The tightly bound Mg(2+)-ADP at the ATP-binding site proved recalcitrant to ligand displacement. Addition of a molar excess of EDTA helped to dislodge the divalent metal ion, promoting the release of ADP and allowing facile exchange with ATP-competitive small-molecule ligands. Many kinases require the presence of a stabilizing ligand in the ATP site for crystallization. This procedure could be useful for developing co-crystallization systems with an exchangeable ligand to enable structure-based drug design of other protein kinases.
Development of a high-throughput crystal structure-determination platform for JAK1 using a novel metal-chelator soaking system.,Caspers NL, Han S, Rajamohan F, Hoth LR, Geoghegan KF, Subashi TA, Vazquez ML, Kaila N, Cronin CN, Johnson E, Kurumbail RG Acta Crystallogr F Struct Biol Commun. 2016 Nov 1;72(Pt 11):840-845. doi:, 10.1107/S2053230X16016356. Epub 2016 Oct 27. PMID:27827355[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Caspers NL, Han S, Rajamohan F, Hoth LR, Geoghegan KF, Subashi TA, Vazquez ML, Kaila N, Cronin CN, Johnson E, Kurumbail RG. Development of a high-throughput crystal structure-determination platform for JAK1 using a novel metal-chelator soaking system. Acta Crystallogr F Struct Biol Commun. 2016 Nov 1;72(Pt 11):840-845. doi:, 10.1107/S2053230X16016356. Epub 2016 Oct 27. PMID:27827355 doi:http://dx.doi.org/10.1107/S2053230X16016356
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