Disease-related mutations in PI3Kγ disrupt regulatory C-terminal dynamics and reveal a path to selective inhibitors
Manoj K. Rathinaswamy,Zied Gaieb,Kaelin D. Fleming,Chiara Borsari,Noah J Harris,Brandon E. Moeller,Matthias P. Wymann,Rommie E. Amaro,John E. Burke +8 more
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Using a combined biochemical/biophysical approach, insight is revealed into regulation of kinase activity, specifically defining how immunodeficiency and oncogenic mutations of R1021 in the C-terminus can inactivate or activate enzyme activity.Citations
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Phosphatidylinositol 3-kinase (PI3K) inhibitors: a recent update on inhibitor design and clinical trials (2016–2020)
TL;DR: In this paper, the PI3K/AKT/mTOR signaling pathway plays a central role in regulating cell growth and proliferation and plays a key role in cell proliferation and cell survival.
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Structure of the phosphoinositide 3-kinase (PI3K) p110γ-p101 complex reveals molecular mechanism of GPCR activation.
Manoj K. Rathinaswamy,Udit Dalwadi,Kaelin D. Fleming,Carson Adams,Jordan T B Stariha,Els Pardon,Minkyung Baek,Oscar Vadas,Frank DiMaio,Jan Steyaert,Scott D. Hansen,Calvin K. Yip,John E. Burke,John E. Burke +13 more
TL;DR: In this paper, the authors report the structure of a heterodimeric PI3Kγ complex, p110γ-p101, which is a unique assembly of catalytic and regulatory subunits.
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The role of PI3Kγ in the immune system: new insights and translational implications
TL;DR: The immunomodulatory properties of phosphoinositide 3-kinase-γ (PI3Kγ) in health and in the context of various diseases, ranging from cardiovascular disease to auto-immunity and cancer, and discusses the therapeutic potential of PI3Kβ inhibitors, which have entered clinical trials for cancer.
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HDX-MS-optimized approach to characterize nanobodies as tools for biochemical and structural studies of class IB phosphoinositide 3-kinases
Manoj K. Rathinaswamy,Kaelin D. Fleming,Udit Dalwadi,Els Pardon,Noah J Harris,Calvin K. Yip,Jan Steyaert,John E. Burke,John E. Burke +8 more
TL;DR: In this paper, the authors describe the characterization of multiple PI3Kγ binding single-chain camelid nanobodies using hydrogen-deuterium exchange (HDX) mass spectrometry (MS).
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Synthesis and bioevaluation of diaryl urea derivatives as potential antitumor agents for the treatment of human colorectal cancer
TL;DR: In this paper , a series of diaryl urea derivatives has been designed and synthesized based on clinical candidate gedatolisib (6aa), and most of the newly synthesized derivatives showed kinase inhibitory and antiproliferative activities within nanomolar and submicromolar level, respectively.
References
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Comparison of simple potential functions for simulating liquid water
TL;DR: In this article, the authors compared the Bernal Fowler (BF), SPC, ST2, TIPS2, TIP3P, and TIP4P potential functions for liquid water in the NPT ensemble at 25°C and 1 atm.
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TL;DR: Coot is a molecular-graphics program designed to assist in the building of protein and other macromolecular models and the current state of development and available features are presented.
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TL;DR: A description is given of Phaser-2.1: software for phasing macromolecular crystal structures by molecular replacement and single-wavelength anomalous dispersion phasing.
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Fast, scalable generation of high‐quality protein multiple sequence alignments using Clustal Omega
Fabian Sievers,Andreas Wilm,David Dineen,Toby J. Gibson,Kevin Karplus,Weizhong Li,Rodrigo Lopez,Hamish McWilliam,Michael Remmert,Johannes Söding,Julie D. Thompson,Desmond G. Higgins +11 more
TL;DR: A new program called Clustal Omega is described, which can align virtually any number of protein sequences quickly and that delivers accurate alignments, and which outperforms other packages in terms of execution time and quality.
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Comparative Protein Modelling by Satisfaction of Spatial Restraints
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PI3Kγ is a molecular switch that controls immune suppression
Megan M. Kaneda,Karen Messer,Natacha Ralainirina,Hongying Li,Christopher J. Leem,Sara Gorjestani,Gyunghwi Woo,Abraham V. Nguyen,Camila C. Figueiredo,Camila C. Figueiredo,Philippe Foubert,Michael C. Schmid,Melissa Pink,David G. Winkler,Matthew Rausch,Vito J. Palombella,Jeffery L. Kutok,Karen McGovern,Kelly A. Frazer,Xuefeng Wu,Michael Karin,Roman Sasik,Ezra E.W. Cohen,Judith A. Varner +23 more