8fe9: Difference between revisions

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-'''Unreleased structure'''
-The entry 8fe9 is ON HOLD
+==Crystal structure of Ack1 kinase K161Q mutant in complex with the selective inhibitor (R)-9b==
+<StructureSection load='8fe9' size='340' side='right'caption='[[8fe9]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8fe9]] 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=8FE9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8FE9 FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=R9B:N-[(1S)-1-BENZYL-2-[(6-CHLORO-2-OXO-1H-QUINOLIN-4-YL)METHYLAMINO]-2-OXO-ETHYL]-4-HYDROXY-2-OXO-1H-QUINOLINE-6-CARBO'>R9B</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=8fe9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8fe9 OCA], [https://pdbe.org/8fe9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8fe9 RCSB], [https://www.ebi.ac.uk/pdbsum/8fe9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8fe9 ProSAT]</span></td></tr>
+</table>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Tyrosine kinases (TKs) play essential roles in signaling processes that regulate cell survival, migration, and proliferation. Dysregulation of tyrosine kinases underlies many disorders, including cancer, cardiovascular and developmental diseases, as well as pathologies of the immune system. Ack1 and Brk are nonreceptor tyrosine kinases (NRTKs) best known for their roles in cancer. Here, we have biochemically characterized novel Ack1 and Brk mutations identified in patients with systemic lupus erythematosus (SLE). These mutations are the first SLE-linked polymorphisms found among NRTKs. We show that two of the mutants are catalytically inactive, while the other three have reduced activity. To understand the structural changes associated with the loss-of-function phenotype, we solved the crystal structure of one of the Ack1 kinase mutants, K161Q. Furthermore, two of the mutated residues (Ack1 A156 and K161) critical for catalytic activity are highly conserved among other TKs, and their substitution in other members of the kinase family could have implications in cancer. In contrast to canonical gain-of-function mutations in TKs observed in many cancers, we report loss-of-function mutations in Ack1 and Brk, highlighting the complexity of TK involvement in human diseases.
-Authors: Paung, Y., Kan, Y., Seeliger, M.S., Miller, W.T.
+Biochemical Studies of Systemic Lupus Erythematosus-Associated Mutations in Nonreceptor Tyrosine Kinases Ack1 and Brk.,Kan Y, Paung Y, Kim Y, Seeliger MA, Miller WT Biochemistry. 2023 Mar 21;62(6):1124-1137. doi: 10.1021/acs.biochem.2c00685. Epub , 2023 Feb 28. PMID:36854171<ref>PMID:36854171</ref>
-Description: Crystal structure of Ack1 kinase K161Q mutant in complex with the selective inhibitor (R)-9b
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Paung, Y]]
+<div class="pdbe-citations 8fe9" style="background-color:#fffaf0;"></div>
-[[Category: Miller, W.T]]
+== References ==
-[[Category: Kan, Y]]
+<references/>
-[[Category: Seeliger, M.S]]
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Kan Y]]
+[[Category: Miller WT]]
+[[Category: Paung Y]]
+[[Category: Seeliger MS]]