David H. Russell
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View article: Dissecting Heterogeneous Populations of Protein-Complex Samples Using Direct Mass Technology
Dissecting Heterogeneous Populations of Protein-Complex Samples Using Direct Mass Technology Open
Charge detection mass spectrometry (CDMS) is an emerging technique for the qualitative analysis of heterogeneous biological samples by individually measuring the charge and m/z of ions to determine their mass. The commercialization of CDMS…
View article: Effects of Hydration on Transthyretin Conformational Dynamics and Oligomerization
Effects of Hydration on Transthyretin Conformational Dynamics and Oligomerization Open
Transthyretin (TTR) is a 56 kDa tetrameric protein complex that transports thyroxine and retinol but can misfold, causing amyloid diseases, such as senile systemic amyloidosis, familial amyloid cardiomyopathy, and familial amyloid polyneur…
View article: Improving the Quadrupole to Ion Mobility Region in a Digital Quadrupole/Ion Mobility/Orbitrap Mass Spectrometer
Improving the Quadrupole to Ion Mobility Region in a Digital Quadrupole/Ion Mobility/Orbitrap Mass Spectrometer Open
A quadrupole/drift tube ion mobility/Orbitrap instrument requires pumping from atmosphere to 10-5 Torr in the quadrupole analyzer region, back to 1 Torr for the drift tube, and a return to 10-5 Torr for the Orbitrap high vacuum region. The…
View article: Roles of Hydration in Protein–Ligand Binding: Passive or Active Participant?
Roles of Hydration in Protein–Ligand Binding: Passive or Active Participant? Open
Hydration is a critical yet often underappreciated factor that influences protein dynamics in solution, with direct effects on structure, stability, and interactions such as ligand binding. Native mass spectrometry (nMS) enables the analys…
View article: Hydration (H<sub>2</sub>O and D<sub>2</sub>O) Dictates the Stabilities and Conformational Entropy of Transthyretin Tetramers
Hydration (H<sub>2</sub>O and D<sub>2</sub>O) Dictates the Stabilities and Conformational Entropy of Transthyretin Tetramers Open
Transthyretin (TTR) is a 56 kDa tetrameric protein complex that plays a key role in transporting thyroxine and retinol. Despite its important biological role, TTR exhibits adverse effects, including disassembly into monomers, dimers, and t…
View article: Molecular Basis for the Activation of <i>Pseudomonas aeruginosa</i> MsbA by Divalent Metals
Molecular Basis for the Activation of <i>Pseudomonas aeruginosa</i> MsbA by Divalent Metals Open
Proteins involved in the biogenesis of lipopolysaccharide (LPS), a lipid exclusive to Gram-negative bacteria, are promising candidates for drug discovery. Specifically, the ABC transporter MsbA plays a crucial role in translocating an LPS …
View article: Allostery without Conformational Change: A Native Mass Spectrometry Perspective
Allostery without Conformational Change: A Native Mass Spectrometry Perspective Open
Native electrospray ionization-mass spectrometry (nESI-MS) enables studies of intact proteins, protein complexes, and protein-ligand complexes. Variable temperature (vT)-nESI-MS, where the temperature of the solution contained in the ESI e…
View article: Transcriptome profiling of prostatic tumours from ENACT trial patients with or without enzalutamide
Transcriptome profiling of prostatic tumours from ENACT trial patients with or without enzalutamide Open
Objectives To evaluate the longitudinal transcriptomic changes that occurred over time in patients from the ENACT trial (ClinicalTrials.gov identifier: NCT02799745). ENACT evaluated patients with low‐ or intermediate‐risk prostate cancer, …
View article: Design and Synthesis of Hetero-Bicephalic Detergents for Native Mass Spectrometry of Membrane Proteins
Design and Synthesis of Hetero-Bicephalic Detergents for Native Mass Spectrometry of Membrane Proteins Open
Native mass spectrometry is playing a central role in characterizing the noncovalent interactions of membrane proteins, enabling the discovery of lipids that regulate membrane protein function and modulate interactions with other molecules…
View article: Revealing Anisotropic Growth of Liraglutide Oligomers by Native Ion Mobility Mass Spectrometry and Molecular Dynamics Simulation
Revealing Anisotropic Growth of Liraglutide Oligomers by Native Ion Mobility Mass Spectrometry and Molecular Dynamics Simulation Open
Oligomerization is an intriguing problem, particularly at the early stages of soluble prefibril oligomer formation, where the growth mechanisms of these species remain difficult to study due to their complexity and heterogeneity. Liragluti…
View article: Dissecting Hidden Liraglutide Oligomerization Pathways via Direct Mass Technology, Electron-Capture Dissociation, and Molecular Dynamics
Dissecting Hidden Liraglutide Oligomerization Pathways via Direct Mass Technology, Electron-Capture Dissociation, and Molecular Dynamics Open
Peptide therapeutics have revolutionized drug design strategies, yet the inherent structural flexibility and conjugated moieties of drug molecules present challenges in discovery, rational design, and manufacturing. Liraglutide, a GLP-1 re…
View article: Allostery Without Conformational Change: A Native Mass Spectrometry Perspective
Allostery Without Conformational Change: A Native Mass Spectrometry Perspective Open
Native electrospray ionization mass spectrometry (nESI-MS) enables studies of intact proteins, protein complexes, and protein-protein and protein-ligand complexes. Variable temperature (vT)-nESI-MS, where the temperature of the solution co…
View article: Unveiling the Hidden: Dissecting Liraglutide Oligomerization Dual Pathways via Direct Mass Technology, Electron-Capture Dissociation, and Molecular Dynamics
Unveiling the Hidden: Dissecting Liraglutide Oligomerization Dual Pathways via Direct Mass Technology, Electron-Capture Dissociation, and Molecular Dynamics Open
Peptide therapeutics have revolutionized drug design strategies, yet the inherent structural flexibility and conjugated moieties of drug molecules present challenges in discovery, rational design, and manufacturing. Liraglutide, a GLP-1 re…
View article: Geriatric Vulnerabilities Among Adults With Heart Failure With Preserved Ejection Fraction
Geriatric Vulnerabilities Among Adults With Heart Failure With Preserved Ejection Fraction Open
Geriatric vulnerabilities across multiple health domains commonly co-occur in adults with HFpEF and are associated with a worse prognosis.
View article: Revealing Anisotropic Growth of Liraglutide Oligomers by Native Ion Mobility Mass Spectrometry and Molecular Dynamics Simulation
Revealing Anisotropic Growth of Liraglutide Oligomers by Native Ion Mobility Mass Spectrometry and Molecular Dynamics Simulation Open
Oligomerization is an intriguing problem, particularly at the early stages of precursor formation, where the mechanisms of oligomer growth are difficult to study due to their complexity and heterogeneity. Liraglutide, a widely used drug fo…
View article: Frataxin Traps Low Abundance Quaternary Structure to Stimulate Human Fe–S Cluster Biosynthesis
Frataxin Traps Low Abundance Quaternary Structure to Stimulate Human Fe–S Cluster Biosynthesis Open
Iron-sulfur clusters are essential protein cofactors synthesized in human mitochondria by an NFS1-ISD11-ACP-ISCU2-FXN assembly complex. Surprisingly, researchers have discovered three distinct quaternary structures for cysteine desulfurase…
View article: Molecular basis for the activation of <i>Pseudomonas aeruginosa</i> MsbA by Zn<sup>2+</sup>
Molecular basis for the activation of <i>Pseudomonas aeruginosa</i> MsbA by Zn<sup>2+</sup> Open
Proteins involved in the biogenesis of lipopolysaccharide (LPS), a lipid exclusive to Gram-negative bacteria, are promising candidates for drug discovery. Specifically, the ABC transporter MsbA plays a crucial role in translocating an LPS …
View article: Temperature-dependence of membrane protein–lipid interactions in membranes
Temperature-dependence of membrane protein–lipid interactions in membranes Open
Membrane protein–lipid interactions, like other biomolecular interactions, are often temperature-sensitive.
View article: Inhibition of Subunit Exchange and N-Finger Rearrangement in SARS-CoV-2 Main Protease by Peptidomimetic Inhibitors
Inhibition of Subunit Exchange and N-Finger Rearrangement in SARS-CoV-2 Main Protease by Peptidomimetic Inhibitors Open
The main protease (Mpro) of SARS-CoV-2 is an essential enzyme for viral replication, making it a critical target for antiviral drug development. While current Mpro inhibitors, such as Paxlovid, focus on active site binding, resistance muta…
View article: Structure and Stabilities of Solution and Gas Phase Protein Complexes
Structure and Stabilities of Solution and Gas Phase Protein Complexes Open
Collision-induced unfolding (CIU) has provided new levels of understanding of the stabilities and structure(s) for gas phase protein and protein complex ions formed by electrospray ionization (ESI). Variable-temperature (vT-ESI) data provi…
View article: Temperature-Dependent Trimethylamine <i>N</i>-Oxide Induced the Formation of Substance P Dimers
Temperature-Dependent Trimethylamine <i>N</i>-Oxide Induced the Formation of Substance P Dimers Open
Interactions of the peptide substance P (SP) (RPKPQQFFGLM-NH2) with trimethylamine N-oxide (TMAO) were investigated by using cryo-ion mobility-mass spectrometry (cryo-IM-MS), variable-temperature (278-358 K) electrospray ionization (vT-ESI…
View article: Native Mass Spectrometry of Membrane Protein–Lipid Interactions in Different Detergent Environments
Native Mass Spectrometry of Membrane Protein–Lipid Interactions in Different Detergent Environments Open
Native mass spectrometry (MS) reveals the role of specific lipids in modulating membrane protein structure and function. Membrane proteins solubilized in detergents are often introduced into the mass spectrometer. However, detergents commo…
View article: Capturing RAS oligomerization on a membrane
Capturing RAS oligomerization on a membrane Open
RAS GTPases associate with the biological membrane where they function as molecular switches to regulate cell growth. Recent studies indicate that RAS proteins oligomerize on membranes, and disrupting these assemblies represents an alterna…
View article: Water Plays Key Roles in Stabilities of Wild Type and Mutant Transthyretin Complexes
Water Plays Key Roles in Stabilities of Wild Type and Mutant Transthyretin Complexes Open
Transthyretin (TTR), a 56 kDa homotetramer that is involved in the transport of thyroxine and retinol, has been linked to amyloidosis through disassembly of tetramers to form monomers, dimers, and trimers that then reassemble into higher o…
View article: Native mass spectrometry of membrane protein-lipid interactions in different detergent environments
Native mass spectrometry of membrane protein-lipid interactions in different detergent environments Open
Native mass spectrometry (MS) is revealing the role of specific lipids in modulating membrane protein structure and function. Membrane proteins solubilized in detergents are often introduced into the mass spectrometer; however, commonly us…