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7l25

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HPK1 IN COMPLEX WITH COMPOUND 18

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Retrieved from "http://52.214.119.220/wiki/index.php/7l25"

Categories: Homo sapiens | Large Structures | Lesburg CA

@@ Line 3: / Line 3: @@
 <StructureSection load='7l25' size='340' side='right'caption='[[7l25]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[7l25]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7L25 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7L25 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[7l25]] 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=7L25 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7L25 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=XHS:6-(2-fluoro-6-methoxyphenyl)-1-[6-(4-methylpiperazin-1-yl)pyridin-2-yl]-1H-pyrazolo[4,3-c]pyridine'>XHS</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.85&#8491;</td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=XHS:6-(2-fluoro-6-methoxyphenyl)-1-[6-(4-methylpiperazin-1-yl)pyridin-2-yl]-1H-pyrazolo[4,3-c]pyridine'>XHS</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=7l25 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7l25 OCA], [https://pdbe.org/7l25 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7l25 RCSB], [https://www.ebi.ac.uk/pdbsum/7l25 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7l25 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[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>
+[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>
-<div style="background-color:#fffaf0;">
-== Publication Abstract from PubMed ==
-Hematopoietic progenitor kinase (HPK1), a negative regulator of TCR-mediated T-cell activation, has been recognized as a novel antitumor immunotherapy target. Structural optimization of kinase inhibitor 4 through a systematic two-dimensional diversity screen of pyrazolopyridines led to the identification of potent and selective compounds. Crystallographic studies with HPK1 revealed a favorable water-mediated interaction with Asp155 and a salt bridge to Asp101 with optimized heterocyclic solvent fronts that were critical for enhanced potency and selectivity. Computational studies of model systems revealed differences in torsional profiles that allowed for these beneficial protein-ligand interactions. Further optimization of molecular properties led to identification of potent and selective reverse indazole inhibitor 36 that inhibited phosphorylation of adaptor protein SLP76 in human PBMC and exhibited low clearance with notable bioavailability in in vivo rat studies.
-Identification of Potent Reverse Indazole Inhibitors for HPK1.,Yu EC, Methot JL, Fradera X, Lesburg CA, Lacey BM, Siliphaivanh P, Liu P, Smith DM, Xu Z, Piesvaux JA, Kawamura S, Xu H, Miller JR, Bittinger M, Pasternak A ACS Med Chem Lett. 2021 Mar 1;12(3):459-466. doi: 10.1021/acsmedchemlett.0c00672., eCollection 2021 Mar 11. PMID:33738073<ref>PMID:33738073</ref>
-From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-</div>
-<div class="pdbe-citations 7l25" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Non-specific serine/threonine protein kinase]]
+[[Category: Lesburg CA]]
-[[Category: Lesburg, C A]]
-[[Category: Hpk1 hematopoietic progenitor kinase]]
-[[Category: Inhibitor complex]]
-[[Category: Transferase]]
-[[Category: Transferase-transferase inhibitor complex]]

7l25

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HPK1 IN COMPLEX WITH COMPOUND 18

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