There's more to death than life: Noncatalytic functions in kinase and pseudokinase signaling.
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A review of the non-catalytic functions of protein kinases can be found in this paper, where the authors consider pseudokinases, proteins that are devoid of enzymatic activity altogether and demonstrate that, beyond conventional notions of kinase function, catalytic activity can be dispensable for biological function.About:
This article is published in Journal of Biological Chemistry.The article was published on 2021-01-01 and is currently open access. It has received 40 citations till now. The article focuses on the topics: Kinase activity & Protein kinase A.read more
Citations
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Journal ArticleDOI
Targeting the Non-Catalytic Functions: a New Paradigm for Kinase Drug Discovery?
TL;DR: The characterized noncatalytic functions of kinases are summarized, and the recent progress on developing small-molecule modulators of the noncatalyst functions of Kinase catalytic functions are highlighted.
Journal ArticleDOI
Blocking Non-enzymatic Functions by PROTAC-Mediated Targeted Protein Degradation.
TL;DR: In this paper , the authors summarize and analyze recent progress in blocking non-enzymatic functions of target proteins by PROTAC-mediated degradation, highlighting representative case studies and discussing the pharmacological features originating from inhibition of the non enzymatic function.
Journal ArticleDOI
Chemical Probes for Understudied Kinases: Challenges and Opportunities.
Ricardo A. M. Serafim,Jonathan M. Elkins,William J. Zuercher,Stefan Laufer,Matthias Gehringer +4 more
TL;DR: In this paper, the authors highlight recent case studies illustrating the development of high-quality chemical probes for less-studied kinases and their application in target validation and discuss the associated challenges and opportunities.
Journal ArticleDOI
Looking lively: emerging principles of pseudokinase signaling.
Joshua B. Sheetz,Mark A. Lemmon +1 more
TL;DR: In this paper , the authors discuss recent structural data on conformational transitions and nucleotide binding by pseudokinases and discuss how biasing this conformational toggle may provide opportunities to target pseudokinase pharmacologically in disease.
Journal ArticleDOI
Structure vs. Function of TRIB1—Myeloid Neoplasms and Beyond
TL;DR: The TRIB1 family of proteins as discussed by the authors plays important roles in differentiation, development, and oncogenesis, and is known to be accessible to small-molecule inhibitors in spite of its inability to bind ATP.
References
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Journal ArticleDOI
Protein polyglutamylation catalyzed by the bacterial calmodulin-dependent pseudokinase SidJ.
Alan Sulpizio,Marena E. Minelli,Min Wan,Paul D Burrowes,Xiaochun Wu,Ethan J. Sanford,Jung-Ho Shin,Byron C. Williams,Michael L. Goldberg,Marcus B. Smolka,Yuxin Mao +10 more
TL;DR: The crystal structure of the Legionella pneumophila effector protein, SidJ, in complex with the eukaryotic Ca2+-binding regulator, calmodulin (CaM), reveals that SidJ contains a protein kinase-like fold domain, which retains a majority of the characteristic kinase catalytic motifs, but SidJ fails to demonstrate kinase activity.
ComponentDOI
Substrate binding allosterically relieves autoinhibition of the pseudokinase TRIB1
Sam A. Jamieson,Zheng Ruan,Abigail E. Burgess,Jack R. Curry,Hamish D McMillan,Jodi L. Brewster,Anita K. Dunbier,Alison D. Axtman,Natarajan Kannan,Peter D. Mace +9 more
TL;DR: A view of pseudokinase regulation with striking parallels to bona fide kinase regulation is offered—by means of the activation loop and αC helix—and the possibility of small molecules targeting either the activation “loop-in” or "loop-out” conformations of Tribbles pseudokinases is raised.
Journal ArticleDOI
Distinct pseudokinase domain conformations underlie divergent activation mechanisms among vertebrate MLKL orthologues
Katherine A Davies,Katherine A Davies,Cheree Fitzgibbon,Samuel N. Young,Sarah E Garnish,Sarah E Garnish,Wayland Yeung,Diane Coursier,Richard W Birkinshaw,Richard W Birkinshaw,Jarrod J. Sandow,Jarrod J. Sandow,Wil I. L. Lehmann,Wil I. L. Lehmann,Lung-Yu Liang,Lung-Yu Liang,Isabelle S Lucet,Isabelle S Lucet,James D. Chalmers,Wayne M. Patrick,Natarajan Kannan,Emma J. Petrie,Emma J. Petrie,Peter E. Czabotar,Peter E. Czabotar,James M. Murphy,James M. Murphy +26 more
TL;DR: The structural determinants of species specificity in necroptosis signaling mediated by the essential necroPTotic effector pseudokinase, Mixed Lineage Kinase Domain-Like (MLKL), are defined.
Journal ArticleDOI
Conformational interconversion of MLKL and disengagement from RIPK3 precede cell death by necroptosis.
Sarah E Garnish,Sarah E Garnish,Yanxiang Meng,Yanxiang Meng,Akiko Koide,Jarrod J. Sandow,Jarrod J. Sandow,Eric Denbaum,Annette V. Jacobsen,Annette V. Jacobsen,Wayland Yeung,Andre L. Samson,Andre L. Samson,Christopher R Horne,Christopher R Horne,Cheree Fitzgibbon,Samuel N. Young,Phoebe P. C. Smith,Andrew I. Webb,Andrew I. Webb,Emma J. Petrie,Emma J. Petrie,Joanne M Hildebrand,Joanne M Hildebrand,Natarajan Kannan,Peter E. Czabotar,Peter E. Czabotar,Shohei Koide,James M. Murphy,James M. Murphy +29 more
TL;DR: In this paper, the pseudokinase domain of MLKL was studied and the crystal structures of two synthetic binding proteins, Monobody-27 and 32, were found to undergo a large conformational change upon activation and disengagement from RIPK3.
Journal ArticleDOI
Divergent kinase regulates membrane ultrastructure of the Toxoplasma parasitophorous vacuole.
Tsebaot Beraki,Xiaoyu Hu,Malgorzata Broncel,Joanna C. Young,William J. O’Shaughnessy,Dominika Borek,Moritz Treeck,Michael L. Reese +7 more
TL;DR: The founding member of the WNG1, phosphorylates parasite proteins that regulate membrane structure, and is therefore required for the proper biogenesis of the Toxoplasma parasitophorous vacuole, a structure essential for the parasite to cause disease.
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