4e4n: Difference between revisions

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-[[Image:4e4n.jpg|left|200px]]
-<!--
+==JAK1 kinase (JH1 domain) in complex with compound 49==
-The line below this paragraph, containing "STRUCTURE_4e4n", creates the "Structure Box" on the page.
+<StructureSection load='4e4n' size='340' side='right'caption='[[4e4n]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[4e4n]] 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=4E4N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4E4N FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0NL:TERT-BUTYL+[(1R,3R)-3-(IMIDAZO[4,5-D]PYRROLO[2,3-B]PYRIDIN-1(6H)-YL)CYCLOPENTYL]CARBAMATE'>0NL</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr>
-{{STRUCTURE_4e4n|  PDB=4e4n  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4e4n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e4n OCA], [https://pdbe.org/4e4n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4e4n RCSB], [https://www.ebi.ac.uk/pdbsum/4e4n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4e4n ProSAT]</span></td></tr>
+</table>
+== 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.
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+A therapeutic rationale is proposed for the treatment of inflammatory diseases, such as rheumatoid arthritis (RA), by specific targeting of the JAK1 pathway. Examination of the preferred binding conformation of clinically effective, pan-JAK inhibitor 1 led to identification of a novel, tricyclic hinge binding scaffold 3. Exploration of SAR through a series of cycloamino and cycloalkylamino analogs demonstrated this template to be highly tolerant of substitution, with a predisposition to moderate selectivity for the JAK1 isoform over JAK2. This study culminated in the identification of sub-nanomolar JAK1 inhibitors such as 22 and 49, having excellent cell potency, good rat pharmacokinetic characteristics, and excellent kinase selectivity. Determination of the binding modes of the series in JAK1 and JAK2 by X-ray crystallography supported the design of analogs to enhance affinity and selectivity.
-===JAK1 kinase (JH1 domain) in complex with compound 49===
+Identification of Imidazo-pyrrolopyridines as Novel and Potent JAK1 Inhibitors.,Kulagowski J J Med Chem. 2012 May 16. PMID:22591402<ref>PMID:22591402</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 4e4n" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_22591402}}, adds the Publication Abstract to the page
+*[[Janus kinase 3D structures|Janus kinase 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 22591402 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_22591402}}
+__TOC__
+</StructureSection>
-==About this Structure==
-[[4e4n]] 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=4E4N OCA].
-==Reference==
-<ref group="xtra">PMID:022591402</ref><references group="xtra"/>
 [[Category: Homo sapiens]]
-[[Category: Non-specific protein-tyrosine kinase]]
+[[Category: Large Structures]]
-[[Category: Eigenbrot, C.]]
+[[Category: Eigenbrot C]]
-[[Category: O-phosphotyrosine]]
-[[Category: Transferase-transferase inhibitor complex]]