7kac
From Proteopedia
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==Crystal structure of HPK1 (MAP4K1) kinase in complex with 5-{[4-{[(1S)-2-HYDROXY-1-PHENYLETHYL]AMINO}-5-(1,3,4-OXADIAZOL-2-YL)PYRIMIDIN-2-YL]AMINO}-3,3-DIMETHYL-2-BENZOFURAN-1(3H)-ONE== | ==Crystal structure of HPK1 (MAP4K1) kinase in complex with 5-{[4-{[(1S)-2-HYDROXY-1-PHENYLETHYL]AMINO}-5-(1,3,4-OXADIAZOL-2-YL)PYRIMIDIN-2-YL]AMINO}-3,3-DIMETHYL-2-BENZOFURAN-1(3H)-ONE== | ||
| - | <StructureSection load='7kac' size='340' side='right'caption='[[7kac]]' scene=''> | + | <StructureSection load='7kac' size='340' side='right'caption='[[7kac]], [[Resolution|resolution]] 1.85Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7KAC OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>[[7kac]] 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=7KAC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KAC FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.85Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=W9D:5-{[4-{[(1S)-2-hydroxy-1-phenylethyl]amino}-5-(1,3,4-oxadiazol-2-yl)pyrimidin-2-yl]amino}-3,3-dimethyl-2-benzofuran-1(3H)-one'>W9D</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=7kac FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kac OCA], [https://pdbe.org/7kac PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kac RCSB], [https://www.ebi.ac.uk/pdbsum/7kac PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kac ProSAT]</span></td></tr> | ||
</table> | </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> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Hematopoietic progenitor kinase 1 (HPK1) is an intracellular kinase that plays an important role in modulating tumor immune response and thus is an attractive target for drug discovery. Crystallization of the wild-type HPK1 kinase domain has been hampered by poor expression in recombinant systems and poor solubility. In this study, yeast surface display was applied to a library of HPK1 kinase-domain variants in order to select variants with an improved expression level and solubility. The HPK1 variant with the most improved properties contained two mutations, crystallized readily in complex with several small-molecule inhibitors and provided valuable insight to guide structure-based drug design. This work exemplifies the benefit of yeast surface display towards engineering crystallizable proteins and thus enabling structure-based drug discovery. | ||
| + | |||
| + | Using yeast surface display to engineer a soluble and crystallizable construct of hematopoietic progenitor kinase 1 (HPK1).,Lau WL, Pearce B, Malakian H, Rodrigo I, Xie D, Gao M, Marsilio F, Chang C, Ruzanov M, Muckelbauer JK, Newitt JA, Lipovsek D, Sheriff S Acta Crystallogr F Struct Biol Commun. 2021 Jan 1;77(Pt 1):22-28. doi:, 10.1107/S2053230X20016015. Epub 2020 Dec 22. PMID:33439152<ref>PMID:33439152</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7kac" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Sheriff S]] | [[Category: Sheriff S]] | ||
Current revision
Crystal structure of HPK1 (MAP4K1) kinase in complex with 5-{[4-{[(1S)-2-HYDROXY-1-PHENYLETHYL]AMINO}-5-(1,3,4-OXADIAZOL-2-YL)PYRIMIDIN-2-YL]AMINO}-3,3-DIMETHYL-2-BENZOFURAN-1(3H)-ONE
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