3eyh: Difference between revisions
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<StructureSection load='3eyh' size='340' side='right'caption='[[3eyh]], [[Resolution|resolution]] 2.00Å' scene=''> | <StructureSection load='3eyh' size='340' side='right'caption='[[3eyh]], [[Resolution|resolution]] 2.00Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3eyh]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[3eyh]] 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=3EYH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3EYH FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IZA:2-TERT-BUTYL-9-FLUORO-3,6-DIHYDRO-7H-BENZ[H]-IMIDAZ[4,5-F]ISOQUINOLINE-7-ONE'>IZA</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=3eyh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3eyh OCA], [https://pdbe.org/3eyh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3eyh RCSB], [https://www.ebi.ac.uk/pdbsum/3eyh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3eyh 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=3eyh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3eyh OCA], [https://pdbe.org/3eyh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3eyh RCSB], [https://www.ebi.ac.uk/pdbsum/3eyh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3eyh 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. | |||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Bamert RS]] | |||
[[Category: Bamert | [[Category: Fantino E]] | ||
[[Category: Fantino | [[Category: Patell O]] | ||
[[Category: Patell | [[Category: Walden PM]] | ||
[[Category: Walden | [[Category: Wang C]] | ||
[[Category: Wang | [[Category: Williams NK]] | ||
[[Category: Williams | |||
Latest revision as of 03:26, 28 December 2023
Crystal structures of JAK1 and JAK2 inhibitor complexesCrystal structures of JAK1 and JAK2 inhibitor complexes
Structural highlights
FunctionJAK1_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. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe Janus kinases (JAKs) are a pivotal family of protein tyrosine kinases (PTKs) that play prominent roles in numerous cytokine signaling pathways, with aberrant JAK activity associated with a variety of hematopoietic malignancies, cardiovascular diseases and immune-related disorders. Whereas the structures of the JAK2 and JAK3 PTK domains have been determined, the structure of the JAK1 PTK domain is unknown. Here, we report the high-resolution crystal structures of the "active form" of the JAK1 PTK domain in complex with two JAK inhibitors, a tetracyclic pyridone 2-t-butyl-9-fluoro-3,6-dihydro-7H-benz[h]-imidaz[4,5-f]isoquinoline-7-one (CMP6) and (3R,4R)-3-[4-methyl-3-[N-methyl-N-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]p iperidin-1-yl]-3-oxopropionitrile (CP-690,550), and compare them with the corresponding JAK2 PTK inhibitor complexes. Both inhibitors bound in a similar manner to JAK1, namely buried deep within a constricted ATP-binding site, thereby providing a basis for the potent inhibition of JAK1. As expected, the mode of inhibitor binding in JAK1 was very similar to that observed in JAK2, highlighting the challenges in developing JAK-specific inhibitors that target the ATP-binding site. Nevertheless, differences surrounding the JAK1 and JAK2 ATP-binding sites were apparent, thereby providing a platform for the rational design of JAK2- and JAK1-specific inhibitors. Dissecting specificity in the Janus kinases: the structures of JAK-specific inhibitors complexed to the JAK1 and JAK2 protein tyrosine kinase domains.,Williams NK, Bamert RS, Patel O, Wang C, Walden PM, Wilks AF, Fantino E, Rossjohn J, Lucet IS J Mol Biol. 2009 Mar 20;387(1):219-32. Epub 2009 Jan 29. PMID:19361440[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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