A5020874937- Mass Spectrometry Techniques and Applications
- Protein Structure and Dynamics
- Pharmacogenetics and Drug Metabolism
- Enzyme Structure and Function
- Pharmaceutical studies and practices
- Heat shock proteins research
- Analytical Chemistry and Chromatography
- Bacteriophages and microbial interactions
- Porphyrin Metabolism and Disorders
- Conservation Techniques and Studies
- RNA and protein synthesis mechanisms
- Amino Acid Enzymes and Metabolism
- Polyamine Metabolism and Applications
- Advanced Proteomics Techniques and Applications
- Antibiotics Pharmacokinetics and Efficacy
- Monoclonal and Polyclonal Antibodies Research
- Metabolomics and Mass Spectrometry Studies
- Pharmacological Effects and Toxicity Studies
- CRISPR and Genetic Engineering
- Aesthetic Perception and Analysis
- Art History and Market Analysis
- Protein purification and stability
- Financial Crisis of the 21st Century
- Cultural Heritage Materials Analysis
- Hepatitis B Virus Studies
Netherlands Organisation for Applied Scientific Research
2023-2024
Rijksmuseum
2018-2023
Pfizer (United States)
2023
Utrecht University
2004-2014
Netherlands Metabolomics Centre
2009-2013
Baylor College of Medicine
2010
Wageningen University & Research
2009
University of Amsterdam
2007
Vrije Universiteit Amsterdam
2006
Institute for Atomic and Molecular Physics
2006
Prokaryotes have evolved multiple versions of an RNA-guided adaptive immune system that targets foreign nucleic acids. In each case, transcripts derived from clustered regularly interspaced short palindromic repeats (CRISPRs) are thought to selectively target invading phage and plasmids in a sequence-specific process involving variable cassette CRISPR-associated ( cas ) genes. The CRISPR locus Pseudomonas aeruginosa (PA14) includes four genes unique conserved microorganisms harboring the...
We modified and optimized a first generation quadrupole time-of-flight (Q-TOF) 1 to perform tandem mass spectrometry on macromolecular protein complexes. The instrument allows isolation subsequent dissociation of high-mass complexes through collisions with argon molecules. modifications the Q-TOF include introduction (1) flow-restricting sleeve around hexapole ion bridge, (2) low-frequency ion-selecting quadrupole, (3) high-pressure collision cell, (4) high-transmission grids in...
The structural analysis of macromolecular functional protein assemblies by contemporary high resolution biology techniques (such as nuclear magnetic resonance, X-ray crystallography, and electron microscopy) is often still challenging. potential a rather new method to generate information, native mass spectrometry, in combination with ion mobility spectrometry (IM-MS), highlighted here. IM-MS allows the assessment gas phase collision cross sections complex ions, which can be related overall...
Antibody profiling: native mass spectrometry analysis of intact antibodies can be achieved with improved speed, sensitivity, and resolution by using a modified orbitrap instrument. Complex mixtures monoclonal resolved their glycan "fingerprints" profiled. Noncovalent interactions are maintained, thus allowing antibody-antigen binding to measured.
Viral capsid assembly, in which viral proteins self-assemble into complexes of well defined architecture, is a fascinating biological process. Although structure and assembly processes have been the subject many excellent structural biology studies past, questions still remain regarding intricate mechanisms that underlie structure, stability, assembly. Here we used native mass spectrometry-based techniques to study Norwalk virus-like particles. detailed information on fully assembled exists,...
The low-density lipoprotein receptor (LDL-R) is a typical example of multidomain protein, for which in vivo folding assumed to occur vectorially from the amino terminus carboxyl terminus. Using pulse-chase approach intact cells, we found instead that newly synthesized LDL-R molecules folded by way “collapsed” intermediates contained non-native disulfide bonds between distant cysteines. most amino-terminal domain acquired its native conformation late during synthesis. Thus, productive cell...
The aim of this study was to develop a method characterize intact soluble monoclonal IgG1 antibody (IgG) oligomers by mass spectrometry.IgG aggregates (dimers, trimers, tetramers and high-molecular-weight oligomers) were created subjecting an IgG formulation several pH jumps. Protein oligomer fractions isolated high performance size exclusion chromatography (HP-SEC), dialyzed against ammonium acetate 6.0 (a spectrometry-compatible volatile buffer), analyzed native electrospray ionization...
The CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated genes) immune system of bacteria and archaea provides acquired resistance against viruses plasmids, by a strategy analogous to RNA-interference. Key components the defense are ribonucleoprotein complexes, composition which appears highly variable in different subtypes. Previous studies combined mass spectrometry, electron microscopy, small angle x-ray scattering demonstrate that E. coli Cascade...
It has been suggested that the bacterial GroEL chaperonin accommodates only one substrate at any given time, due to conformational changes both cis and trans ring are induced upon binding. Using electrospray ionization mass spectrometry, we show indeed binds molecule of model Rubisco. In contrast, capsid protein bacteriophage T4, a natural substrate, can occupy rings simultaneously. As these substrates similar size, data indicate each induces distinct in chaperonin. The distinctive binding...
Nowadays, mass spectrometry plays an important role in structural biology. At one end it can be used to investigate intact protein complexes, providing details about the complex composition, topology, stability, and dynamics, whereas at other protein's identity possible modifications visualized using proteomics approaches. Combining all this information allows generation of detailed models for functional biological assemblies. Here, a perspective on application native biology is presented....
Abstract Electrospray ionization mass spectrometry (ESI‐MS) is a valuable tool in structural biology for investigating globular proteins and their biomolecular interactions. During the electrospray process, become desolvated multiply charged, which may influence structure. Reducing net charge obtained during process be relevant studying proteins. In this report we demonstrate effect of series inorganic organic gas‐phase bases on number charges that protein complexes attain. Solution...
The mitochondrial flavoenzyme l-galactono-γ-lactone dehydrogenase (GALDH) catalyzes the ultimate step of vitamin C biosynthesis in plants. We found that recombinant GALDH from Arabidopsis (Arabidopsis thaliana) is inactivated by hydrogen peroxide due to selective oxidation cysteine (Cys)-340, located cap domain. Electrospray ionization mass spectrometry revealed partial reversible oxidative modification Cys-340 involves sequential formation sulfenic, sulfinic, and sulfonic acid states....
Native mass spectrometry (native MS) gives information about the composition, topological arrangements, dynamics, and structural properties of protein complexes. The range is principally unlimited highly dynamic, allowing detection small subunits large complexes within same measurement. amount needed for an analysis is, compared to most other biology methods, very low. This unit provides introduction native MS. It starts with explanation basic method details on how measure intact proteins...
3-Hydroxybenzoate 6-hydroxylase (3HB6H) from Rhodococcus jostii RHA1 is a dimeric flavoprotein that catalyzes the NADH- and oxygen-dependent para-hydroxylation of 3-hydroxybenzoate to 2,5-dihydroxybenzoate. In this study, we report crystal structure 3HB6H as expressed in Escherichia coli. The overall fold similar p-hydroxybenzoate hydroxylase other aromatic hydroxylases. Unexpectedly, lipid ligand bound each monomer. Mass spectral analysis identified mixture phosphatidylglycerol...
The increasing role of accelerator mass spectrometry (AMS) in biomedical research necessitates modernization the traditional sample handling process. AMS was originally developed and used for carbon dating, therefore focusing on a very high precision but with comparably low throughput. Here, we describe combination automated combustion an elemental analyzer (EA) online coupled to via dedicated interface. This setup allows direct radiocarbon measurements over 70 samples daily by AMS. No...
Nano-electrospray ionization mass spectrometry (ESI-MS) was used to analyze hydrogen/deuterium (H/D) exchange properties of transmembrane peptides with varying length and composition. Synthetic were a general acetyl-GW<sub>2</sub>(LA)<sub>n</sub>LW<sub>2</sub>A-ethanolamine sequence. These incorporated in large unilamellar vesicles 1,2-dimyristoyl-<i>sn</i>-glycero-3-phosphocholine. The diluted buffered deuterium oxide, the H/D after different incubation times directly analyzed by means...