Please use this identifier to cite or link to this item: 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
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