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https://doi.org/10.1038/ncomms9681
Title: | An in cellulo-derived structure of PAK4 in complex with its inhibitor Inka1 | Authors: | Baskaran, Y Ang, K.C Anekal, P.V Chan, W.L Grimes, J.M Manser, E Robinson, R.C |
Keywords: | adenosine triphosphate Inka1 protein p21 activated kinase 4 phosphotransferase inhibitor unclassified drug adenosine triphosphate Inka protein, human p21 activated kinase PAK4 protein, human protein binding signal peptide cells and cell components crystal structure enzyme activity inhibitor mammal metazoan protein animal cell Article controlled study crystal structure enzyme active site human human cell nonhuman protein binding protein structure animal chemistry Chlorocebus aethiops confocal microscopy COS cell line crystallization Escherichia coli HEK293 cell line HeLa cell line immunoprecipitation in vitro study metabolism protein tertiary structure tumor cell line X ray crystallography Mammalia Metazoa Adenosine Triphosphate Animals Catalytic Domain Cell Line, Tumor Cercopithecus aethiops COS Cells Crystallization Crystallography, X-Ray Escherichia coli HEK293 Cells HeLa Cells Humans Immunoprecipitation In Vitro Techniques Intracellular Signaling Peptides and Proteins Microscopy, Confocal p21-Activated Kinases Protein Binding Protein Structure, Tertiary |
Issue Date: | 2015 | Publisher: | Nature Publishing Group | Citation: | Baskaran, Y, Ang, K.C, Anekal, P.V, Chan, W.L, Grimes, J.M, Manser, E, Robinson, R.C (2015). An in cellulo-derived structure of PAK4 in complex with its inhibitor Inka1. Nature Communications 6 : 8681. ScholarBank@NUS Repository. https://doi.org/10.1038/ncomms9681 | Abstract: | PAK4 is a metazoan-specific kinase acting downstream of Cdc42. Here we describe the structure of human PAK4 in complex with Inka1, a potent endogenous kinase inhibitor. Using single mammalian cells containing crystals 50 ?m in length, we have determined the in cellulo crystal structure at 2.95 Å resolution, which reveals the details of how the PAK4 catalytic domain binds cellular ATP and the Inka1 inhibitor. The crystal lattice consists only of PAK4-PAK4 contacts, which form a hexagonal array with channels of 80 Å in diameter that run the length of the crystal. The crystal accommodates a variety of other proteins when fused to the kinase inhibitor. Inka1-GFP was used to monitor the process crystal formation in living cells. Similar derivatives of Inka1 will allow us to study the effects of PAK4 inhibition in cells and model organisms, to allow better validation of therapeutic agents targeting PAK4. © 2015 Macmillan Publishers Limited. All rights reserved. | Source Title: | Nature Communications | URI: | https://scholarbank.nus.edu.sg/handle/10635/175462 | ISSN: | 20411723 | DOI: | 10.1038/ncomms9681 |
Appears in Collections: | Staff Publications Elements |
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