- Mass Spectrometry Techniques and Applications
- Analytical Chemistry and Chromatography
- Metabolomics and Mass Spectrometry Studies
- Protein Structure and Dynamics
- Advanced Proteomics Techniques and Applications
- Atomic and Molecular Physics
- Fullerene Chemistry and Applications
- Ion-surface interactions and analysis
- Protein purification and stability
- Monoclonal and Polyclonal Antibodies Research
- Plant Parasitism and Resistance
- Advanced Chemical Physics Studies
- Protein Tyrosine Phosphatases
- DNA and Nucleic Acid Chemistry
- Proteoglycans and glycosaminoglycans research
- Pancreatic function and diabetes
- Hemoglobin structure and function
- Parkinson's Disease Mechanisms and Treatments
- Bacterial Genetics and Biotechnology
- Polydiacetylene-based materials and applications
- ATP Synthase and ATPases Research
- Enzyme Catalysis and Immobilization
- Light effects on plants
- Enzyme Structure and Function
- Photochromic and Fluorescence Chemistry
The Graduate Center, CUNY
2016-2025
CUNY Advanced Science Research Center
2016-2025
City University of New York
2016-2024
New York Proton Center
2024
University of Massachusetts Amherst
2007-2018
Wichita State University
2017
Amherst College
2012
Biogen (United States)
2008
Institute of Physics of Molecules and Crystals
2001-2006
Russian Academy of Sciences
2002
Melanins are a family of heterogeneous polymeric pigments that provide ultraviolet (UV) light protection, structural support, coloration, and free radical scavenging. Formed by oxidative oligomerization catecholic small molecules, the physical properties melanins influenced covalent noncovalent disorder. We report use tyrosine-containing tripeptides as tunable precursors for pigments. In these structures, phenols presented in (supra-)molecular context dictated positions amino acids peptide...
Multiple charging is an intrinsic feature of electrospray ionization (ESI) macromolecules. While multiple factors influence the appearance protein ion charge state distributions in ESI mass spectra, physical dimensions molecules solution are major determinants extent charging. This article reviews information that can be obtained by analyzing ionic MS, as well potential pitfalls and limitations this powerful technique. We also discuss future areas growth with particular emphasis on...
Electron-transfer dissociation (ETD) is evaluated as a technique to provide local information on higher order structure and dynamics of whole protein molecule. Isotopic labeling highly flexible segments model 18 kDa carried out in solution under mildly denaturing conditions by means hydrogen/deuterium exchange (HDX), followed transfer intact ions the gas phase electrospray ionization, mass-selection precursor ion for subsequent reactions with fluoranthene radical anions. The ETD process...
Hydrogen/deuterium exchange (HDX) combined with mass spectrometry (MS) detection has matured in recent years to become a powerful tool structural biology and biophysics. Several limitations of this technique can will be addressed by tapping into the ever expanding arsenal methods manipulate ions gas phase offered spectrometry.
Maturation of metabolomics has brought a deeper appreciation for the importance isomeric identity lipids to their biological role, mirroring that proteoforms in proteomics. However, full characterization lipid isomerism been thwarted by paucity rapid and effective analytical tools. A novel approach is ion mobility spectrometry (IMS) particularly differential or field asymmetric waveform IMS (FAIMS) at high electric fields, which more orthogonal mass spectrometry. Here we broadly explore...
Abstract Conformational heterogeneity of α‐synuclein was studied with electrospray ionization mass spectrometry by analyzing protein ion charge state distributions, where the extent multiple charging reflects compactness conformations in solution. Although lacks a single well‐defined structure under physiological conditions, it found to sample four distinct conformational states, ranging from highly structured one random coil. The compact is present across entire range conditions tested (pH...
Protein tyrosine phosphatase 1B (PTP1B) is a validated therapeutic target for obesity, diabetes, and certain types of cancer. In particular, allosteric inhibitors hold potential use, but an incomplete understanding conformational dynamics allostery in this protein has hindered their development. Here, we interrogate solution responses PTP1B using high-resolution hydrogen-deuterium exchange mass spectrometry (HDX-MS), emerging powerful biophysical technique. Using HDX-MS, obtain detailed map...
Mass spectrometry plays a very visible role in biopharmaceutical industry, although its use development, characterization, and quality control of protein drugs is mostly limited to the analysis covalent structure (amino acid sequence post-translational modifications). Despite centrality conformation biological activity, stability, safety products, expanding arsenal mass spectrometry-based methods that are currently available probe higher order conformational dynamics biopolymers did not,...
Unlike small-molecule drugs, the conformational properties of protein biopharmaceuticals in solution are influenced by a variety factors that not solely defined their covalent chemical structure. Since conformation (or higher order structure) is major modulator its biological activity, ability to detect changes both structure and dynamics protein, induced an array extrinsic factors, central importance producing, purifying, formulating commercial biopharmaceutical with consistent therapeutic...
Abstract Lipid shuttling between neurons and glia contributes to the development, function, stress responses of nervous system. To understand how a neuron acquires its lipid supply from specific lipoproteins their receptors, we perform combined genetic, transcriptome, biochemical analyses in developing Drosophila larval brain. Here report, astrocyte-derived secreted lipocalin Glial Lazarillo (GLaz), homolog human Apolipoprotein D (APOD), neuronal receptor, brain-specific short isoforms...
Abstract Water‐responsive (WR) materials that reversibly deform in response to humidity changes show great potential for developing muscle‐like actuators miniature and biomimetic robotics. Here, it is presented Bacillus (B.) subtilis’ peptidoglycan (PG) exhibits WR actuation energy power densities reaching 72.6 MJ m −3 9.1 MW , respectively, orders of magnitude higher than those frequently used actuators, such as piezoelectric dielectric elastomers. PG can much 27.2% within 110 ms, its...
The ability to monitor protein aggregation at the molecular level is critical for progress in many areas of life sciences ranging from understanding mechanisms amyloidosis and etiology conformational diseases development safe efficient biopharmaceutical products. Despite spectacular recent years, aspects aggregating proteins behavior remain unclear because extreme difficulty tracking evolution these notoriously complex heterogeneous systems. Here, we introduce a mass spectrometry-based...
Molecular chaperones have an essential role for the maintenance of a balanced protein homeostasis. Here, we investigate how kinases are recruited and loaded to Hsp90-Cdc37 complex, first step during Hsp90-mediated chaperoning that leads enhanced client kinase stability activation. We show conformational dynamics all partners is critical feature underlying loading mechanism. The kinome co-chaperone Cdc37 exists primarily in dynamic extended conformation but samples low-populated, well-defined...
Significance Structure and dynamic features of nonnative protein conformations are critically important for a variety processes, such as folding, recognition, binding, aggregation, enzyme catalysis to name just few. Nevertheless, detailed structural characterization these elusive species is difficult, because they almost always coexist in equilibrium with other conformers cannot be isolated prior analysis. As result, most studies report that averaged across the entire ensemble, rather than...
Heparin is a densely charged polysaccharide, which best known for its anticoagulant activity, although it also modulates plethora of other biological processes. Unlike biopolymers whose synthesis strictly controlled by unique genetic template, heparin molecules exhibit remarkable degree structural heterogeneity, poses serious challenge studies heparin−protein interactions. This analytical often dealt with reducing the enormous repertoire to model small molecule. In this paper, we describe...