8fko

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'''Unreleased structure'''
 
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The entry 8fko is ON HOLD until Paper Publication
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==Crystal structure of HPK1 kinase domain T165E,S171E phosphomimetic mutant in complex with 3-{4-[(2S,5R)-5-Amino-2-methylpiperidin-1-yl]-6-chloro-7H-pyrrolo[2,3-d]pyrimidin-5-yl}benzonitrile==
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<StructureSection load='8fko' size='340' side='right'caption='[[8fko]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[8fko]] is a 6 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=8FKO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8FKO FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=Y3O:(3P)-3-{4-[(2S,5R)-5-amino-2-methylpiperidin-1-yl]-6-chloro-7H-pyrrolo[2,3-d]pyrimidin-5-yl}benzonitrile'>Y3O</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8fko FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8fko OCA], [https://pdbe.org/8fko PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8fko RCSB], [https://www.ebi.ac.uk/pdbsum/8fko PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8fko ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/M4K1_HUMAN M4K1_HUMAN] Serine/threonine-protein kinase, which may play a role in the response to environmental stress. Appears to act upstream of the JUN N-terminal pathway. May play a role in hematopoietic lineage decisions and growth regulation. Able to autophosphorylate.<ref>PMID:24362026</ref> <ref>PMID:8824585</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Immune activating agents represent a valuable class of therapeutics for the treatment of cancer. An area of active research is expanding the types of these therapeutics that are available to patients via targeting new biological mechanisms. Hematopoietic progenitor kinase 1 (HPK1) is a negative regulator of immune signaling and a target of high interest for the treatment of cancer. Herein, we present the discovery and optimization of novel amino-6-aryl pyrrolopyrimidine inhibitors of HPK1 starting from hits identified via virtual screening. Key components of this discovery effort were structure-based drug design aided by analyses of normalized B-factors and optimization of lipophilic efficiency.
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Authors: McTigue, M., Johnson, E., Cronin, C.
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Design and Synthesis of Functionally Active 5-Amino-6-Aryl Pyrrolopyrimidine Inhibitors of Hematopoietic Progenitor Kinase 1.,Gallego RA, Bernier L, Chen H, Cho-Schultz S, Chung L, Collins M, Del Bel M, Elleraas J, Costa Jones C, Cronin CN, Edwards M, Fang X, Fisher T, He M, Hoffman J, Huo R, Jalaie M, Johnson E, Johnson TW, Kania RS, Kraus M, Lafontaine J, Le P, Liu T, Maestre M, Matthews J, McTigue M, Miller N, Mu Q, Qin X, Ren S, Richardson P, Rohner A, Sach N, Shao L, Smith G, Su R, Sun B, Timofeevski S, Tran P, Wang S, Wang W, Zhou R, Zhu J, Nair SK J Med Chem. 2023 Mar 20. doi: 10.1021/acs.jmedchem.2c02038. PMID:36940470<ref>PMID:36940470</ref>
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Description: Crystal structure of HPK1 kinase domain T165E,S171E phosphomimetic mutant in complex with 3-{4-[(2S,5R)-5-Amino-2-methylpiperidin-1-yl]-6-chloro-7H-pyrrolo[2,3-d]pyrimidin-5-yl}benzonitrile
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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[[Category: Mctigue, M]]
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<div class="pdbe-citations 8fko" style="background-color:#fffaf0;"></div>
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[[Category: Cronin, C]]
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== References ==
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[[Category: Johnson, E]]
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Cronin C]]
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[[Category: Johnson E]]
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[[Category: McTigue M]]

Revision as of 06:31, 7 April 2023

Crystal structure of HPK1 kinase domain T165E,S171E phosphomimetic mutant in complex with 3-{4-[(2S,5R)-5-Amino-2-methylpiperidin-1-yl]-6-chloro-7H-pyrrolo[2,3-d]pyrimidin-5-yl}benzonitrile

PDB ID 8fko

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