František Filandr

Conformational changes in insulin receptor illuminated by live-cell linear dichroism imaging and a FLIP biosensor

Alina Sakhi, Anna Kertisová, Marta Lubos, Paul Miclea et autres

Abstract Insulin receptor (IR) is a tyrosine kinase involved in vital cellular signaling processes related to glucose metabolism and cell growth. Detailed understanding of molecular mechanisms of IR signaling is important for improved treatments of diabetes and related disorders. Although many aspects …

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Beyond traditional strain-promoted azide–alkyne cycloadditions by achieving orthogonality and rapid kinetics with fluoroalkyl azides

Matúš Tomčo, Veronika Šlachtová, Milan Vrábel, Jialu Li et autres

Strain-promoted azide–alkyne cycloaddition (SPAAC) is a cornerstone of bioorthogonal chemistry, offering metal-free and biocompatible ligation for applications ranging from bioconjugation to live-cell imaging. However, its relatively slow kinetics and limited selectivity hinder the simultaneous labelling of multiple targets. Here, we report on …

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Targeting the Membrane‐Embedded Rhomboid Protease GlpG: A Multimodal Strategy for Inhibitor Discovery and Mechanistic Insight

Claudia Bohg, Yurii Dubanych, Spyridon Kosteletos, Taoran Xiao et autres

ABSTRACT Rhomboid proteases, a class of intramembrane proteases characterized by a Ser‐His catalytic dyad, have recently emerged as promising therapeutic targets. While inhibitors for soluble serine proteases have been extensively studied, the spectrum of potent rhomboid protease inhibitor chemotypes is limited to …

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Targeting the Membrane‐Embedded Rhomboid Protease GlpG: A Multimodal Strategy for Inhibitor Discovery and Mechanistic Insight

Claudia Bohg, Yurii Dubanych, Spyridon Kosteletos, Taoran Xiao et autres

ABSTRACT Rhomboid proteases, a class of intramembrane proteases characterized by a Ser‐His catalytic dyad, have recently emerged as promising therapeutic targets. While inhibitors for soluble serine proteases have been extensively studied, the spectrum of potent rhomboid protease inhibitor chemotypes is limited to …

de, cz (code pays fourni par la source)

Targeting the Membrane‐Embedded Rhomboid Protease GlpG: A Multimodal Strategy for Inhibitor Discovery and Mechanistic Insight

Claudia Bohg, Yurii Dubanych, Spyridon Kosteletos, Taoran Xiao et autres

Rhomboid proteases, a class of intramembrane proteases characterized by a Ser‐His catalytic dyad, have recently emerged as promising therapeutic targets. While inhibitors for soluble serine proteases have been extensively studied, the spectrum of potent rhomboid protease inhibitor chemotypes is limited to active‐site …

Beyond Traditional SPAAC: Achieving Orthogonality and Rapid Kinetics with Fluoroalkyl Azides

Matúš Tomčo, Veronika Šlachtová, Milan Vrábel, Jialu Li et autres

Strain-promoted azide–alkyne cycloaddition (SPAAC) is a cornerstone of bioorthogonal chemistry, offering metal-free and biocompatible ligation for applications ranging from bioconjugation to live-cell imaging. However, its relatively slow kinetics and limited selectivity hinder the simultaneous labelling of multiple targets. Here, we report on …

cz (code pays fourni par la source)

BRAF oncogenic mutants evade autoinhibition through a common mechanism

Hugo Lavoie, Ting Jin, Driss Lajoie, Marion Décossas et autres

Uncontrolled activation of the rat sarcoma (RAS)-extracellular signal-regulated kinase (ERK) pathway drives tumor growth, often because of oncogenic BRAF mutations. BRAF regulation, involving monomeric autoinhibition and activation by dimerization, has been intensely scrutinized, but mechanisms enabling oncogenic mutants to evade regulation remain …

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Examining Instrumental Factors Influencing the Performance of Data-Independent Acquisition Methods in Hydrogen/Deuterium Exchange Mass Spectrometry

František Filandr, Morgan Hepburn, Vladimir Sarpe, D. Alex Crowder et autres

Hydrogen/deuterium exchange mass spectrometry (HX-MS) is a method used to study solution-phase protein structure and dynamics. Despite its many applications, HX-MS is limited in throughput because manual data analysis is still the norm. We previously developed HX-MS 2 technology to add a …

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Recommendations for Automating Hydrogen/Deuterium Exchange Mass Spectrometry Measurements using Data-Independent Acquisition Methods

František Filandr, Morgan Hepburn, Vladimir Sarpe, D. Alex Crowder et autres

Hydrogen/deuterium exchange mass spectrometry (HX-MS) is a method used to study solution-phase protein structure and dynamics. Despite its many applications, HX-MS is limited in throughput because manual data analysis is still the norm. We previously developed HX-MS2 technology to add a second …

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Author Correction: Automating data analysis for hydrogen/deuterium exchange mass spectrometry using data-independent acquisition methodology

František Filandr, Vladimir Sarpe, Shaunak Raval, D. Alex Crowder et autres

The original version of this Article omitted the funding source for some authors: “J.A.T. and S.L.M. were funded in part by National Institutes of Health (NIH) grant P01 CA092584, and J.A.T. and A.S. were funded in part by R35 CA220430 and a …

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The HisRS-like domain of GCN2 is a pseudoenzyme that can bind uncharged tRNA

Jay Z. Yin, Alexander F. A. Keszei, Scott Houliston, František Filandr et autres

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Automating data analysis for hydrogen/deuterium exchange mass spectrometry using data-independent acquisition methodology

František Filandr, Vladimir Sarpe, Shaunak Raval, D. Alex Crowder et autres

Abstract We present a hydrogen/deuterium exchange workflow coupled to tandem mass spectrometry (HX-MS 2 ) that supports the acquisition of peptide fragment ions alongside their peptide precursors. The approach enables true auto-curation of HX data by mining a rich set of deuterated …

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