6vnv
From Proteopedia
(Difference between revisions)
| Line 3: | Line 3: | ||
<StructureSection load='6vnv' size='340' side='right'caption='[[6vnv]], [[Resolution|resolution]] 2.15Å' scene=''> | <StructureSection load='6vnv' size='340' side='right'caption='[[6vnv]], [[Resolution|resolution]] 2.15Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[6vnv]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VNV OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6VNV FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6vnv]] 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=6VNV OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6VNV FirstGlance]. <br> |
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=R4Y:(1S,2S)-2-cyano-N-[(1S,5R)-3-(5-fluoro-2-{[1-(2-hydroxyethyl)-1H-pyrazol-4-yl]amino}pyrimidin-4-yl)-3-azabicyclo[3.1.0]hexan-1-yl]cyclopropane-1-carboxamide'>R4Y</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=R4Y:(1S,2S)-2-cyano-N-[(1S,5R)-3-(5-fluoro-2-{[1-(2-hydroxyethyl)-1H-pyrazol-4-yl]amino}pyrimidin-4-yl)-3-azabicyclo[3.1.0]hexan-1-yl]cyclopropane-1-carboxamide'>R4Y</scene></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='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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TYK2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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='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://proteopedia.org/fgij/fg.htm?mol=6vnv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vnv OCA], [http://pdbe.org/6vnv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6vnv RCSB], [http://www.ebi.ac.uk/pdbsum/6vnv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6vnv ProSAT]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6vnv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vnv OCA], [http://pdbe.org/6vnv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6vnv RCSB], [http://www.ebi.ac.uk/pdbsum/6vnv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6vnv ProSAT]</span></td></tr> | ||
| Line 13: | Line 14: | ||
== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/TYK2_HUMAN TYK2_HUMAN]] Probably involved in intracellular signal transduction by being involved in the initiation of type I IFN signaling. Phosphorylates the interferon-alpha/beta receptor alpha chain.<ref>PMID:7526154</ref> | [[http://www.uniprot.org/uniprot/TYK2_HUMAN TYK2_HUMAN]] Probably involved in intracellular signal transduction by being involved in the initiation of type I IFN signaling. Phosphorylates the interferon-alpha/beta receptor alpha chain.<ref>PMID:7526154</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Herein, we disclose a new series of TYK2/ JAK1 inhibitors based upon a 3.1.0 azabicyclic substituted pyrimidine scaffold. We illustrate the use of structure-based drug design for the initial design and subsequent optimization of this series of compounds. One advanced example 19 met program objectives for potency, selectivity and ADME, and demonstrated oral activity in the adjuvant-induced arthritis rat model. | ||
| + | |||
| + | Design and optimization of a series of 4-(3-azabicyclo[3.1.0]hexan-3-yl)pyrimidin-2-amines: Dual inhibitors of TYK2 and JAK1.,Fensome A, Ambler CM, Arnold E, Banker ME, Clark JD, Dowty ME, Efremov IV, Flick A, Gerstenberger BS, Gifford RS, Gopalsamy A, Hegen M, Jussif J, Limburg DC, Lin TH, Pierce BS, Sharma R, Trujillo JI, Vajdos FF, Vincent F, Wan ZK, Xing L, Yang X, Yang X Bioorg Med Chem. 2020 May 15;28(10):115481. doi: 10.1016/j.bmc.2020.115481. Epub , 2020 Mar 31. PMID:32253095<ref>PMID:32253095</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6vnv" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Human]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Non-specific protein-tyrosine kinase]] | [[Category: Non-specific protein-tyrosine kinase]] | ||
Revision as of 06:12, 22 April 2020
Crystal structure of TYK2 kinase with compound 14
| |||||||||||
