keyword
MENU ▼
Read by QxMD icon Read
search

Hydrogen exchange mass spectrometry

keyword
https://www.readbyqxmd.com/read/27903652/prepore-stability-controls-productive-folding-of-the-bam-independent-multimeric-outer-membrane-secretin-puld
#1
Ingrid Guilvout, Sébastien Brier, Mohamed Chami, Véronique Hourdel, Olivera Francetic, Anthony P Pugsley, Julia Chamot-Rooke, Gerard H M Huysmans
Members of a group of multimeric secretion pores that assemble independently of any known membrane-embedded insertase in Gram-negative bacteria fold into a prepore before membrane-insertion occurs. The mechanisms and the energetics that drive the folding of these proteins are poorly understood. Here, equilibrium unfolding and hydrogen/deuterium exchange monitored by mass spectrometry indicated that a loss of 4-5 kJ/mol/protomer in the N3-domain that is peripheral to the membrane-spanning C-domain in the dodecameric secretin PulD, the founding member of this class, prevents pore formation by destabilizing the prepore into a poorly structured dodecamer as visualized by electron microscopy...
November 30, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27892738/methodological-approaches-and-insights-on-protein-aggregation-in-biological-systems
#2
Paulo Bastos, Fábio Trindade, Adelino Leite-Moreira, Inês Falcão-Pires, Rita Ferreira, Rui Vitorino
The proper folding of native proteins is critical and dynamic, but inherently unstable. Therefore, proteins eventually end up adopting misfolded conformations which compromise their function and may even trigger aggregation. Risk factors for neurodegenerative, metabolic and heart diseases compromise cellular protein quality-control systems, promoting protein aggregation. Multiple protein post-translational modifications dynamically regulate protein aggregation and disaggregation in a very complex, intricate and delicate balance...
November 28, 2016: Expert Review of Proteomics
https://www.readbyqxmd.com/read/27889293/stability-behaviour-of-antiretroviral-drugs-and-their-combinations-5-characterization-of-novel-degradation-products-of-abacavir-sulfate-by-mass-and-nuclear-magnetic-resonance-spectrometry
#3
Moolchand Kurmi, Archana Sahu, Saranjit Singh
In the present study, degradation behaviour of abacavir sulfate was evaluated in solution and solid stress conditions. Solution state studies resulted in formation of eleven degradation products; of which two were also formed on solid stress. The same were separated by high performance liquid chromatography. They were characterized using liquid chromatography-high resolution mass spectrometry, liquid chromatography-multistage mass spectrometry and hydrogen/deuterium exchange mass spectrometry data. Additionally, seven degradation products were isolated and subjected to 1D and 2D nuclear magnetic resonance studies for their structural confirmation...
November 5, 2016: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/27879668/structure-functional-basis-of-ion-transport-in-sodium-calcium-exchanger-ncx-proteins
#4
REVIEW
Moshe Giladi, Reut Shor, Michal Lisnyansky, Daniel Khananshvili
The membrane-bound sodium-calcium exchanger (NCX) proteins shape Ca(2+) homeostasis in many cell types, thus participating in a wide range of physiological and pathological processes. Determination of the crystal structure of an archaeal NCX (NCX_Mj) paved the way for a thorough and systematic investigation of ion transport mechanisms in NCX proteins. Here, we review the data gathered from the X-ray crystallography, molecular dynamics simulations, hydrogen-deuterium exchange mass-spectrometry (HDX-MS), and ion-flux analyses of mutants...
November 22, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27879053/n-arylsulfonyl-indolines-as-retinoic-acid-receptor-related-orphan-receptor%C3%A2-%C3%AE-ror%C3%AE-agonists
#5
Christelle Doebelin, Rémi Patouret, Ruben D Garcia-Ordonez, Mi Ra Chang, Venkatasubramanian Dharmarajan, Dana S Kuruvilla, Scott J Novick, Li Lin, Michael D Cameron, Patrick R Griffin, Theodore M Kamenecka
The nuclear retinoic acid receptor-related orphan receptor γ (RORγ; NR1F3) is a key regulator of inflammatory gene programs involved in T helper 17 (TH 17) cell proliferation. As such, synthetic small-molecule repressors (inverse agonists) targeting RORγ have been extensively studied for their potential as therapeutic agents for various autoimmune diseases. Alternatively, enhancing TH 17 cell proliferation through activation (agonism) of RORγ may boost an immune response, thereby offering a potentially new approach in cancer immunotherapy...
November 23, 2016: ChemMedChem
https://www.readbyqxmd.com/read/27872189/biophysical-evidence-for-intrinsic-disorder-in-the-c-terminal-tails-of-the-egfr-and-her3-receptor-tyrosine-kinases
#6
Theodore R Keppel, Kwabena Sarpong, Elisa M Murray, John Monsey, Jian Zhu, Ron Bose
The EGFR/ErbB family of receptor tyrosine kinases includes oncogenes important in the progression of breast and other cancers and they are targets for many drug development strategies. Each member of the ErbB family possesses a unique, structurally uncharacterized C-terminal tail that plays an important role in autophosphorylation and signal propagation. To determine if these C-terminal tails are intrinsically disordered regions, we conducted a battery of biophysical experiments on the EGFR and HER3 tails. Using hydrogen/deuterium exchange mass spectrometry, we measured the conformational dynamics of intracellular half constructs and compared the tails to the ordered kinase domains...
November 21, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27870250/new-insights-into-interactions-between-the-nucleotide-binding-domain-of-cftr-and-keratin-8
#7
Aiswarya Premchandar, Anna Kupniewska, Arkadiusz Bonna, Grazyna Faure, Tomasz Fraczyk, Ariel Roldan, Brice Hoffmann, Mélanie Faria da Cunha, Harald Herrmann, Gergely L Lukacs, Aleksander Edelman, Michał Dadlez
The intermediate filament protein keratin 8 (K8) interacts with the nucleotide-binding domain 1 (NBD1) of the cystic fibrosis transmembrane regulator (CFTR) with phenylalanine 508 deletion (ΔF508), and this interaction hampers the biogenesis of functional ΔF508-CFTR and its insertion into the plasma membrane. Interruption of this interaction may constitute a new therapeutic target for cystic fibrosis patients bearing the ΔF508 mutation. Here we aimed to determine the binding surface between these two proteins, to facilitate the design of the interaction inhibitors...
November 21, 2016: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/27851982/interdomain-electron-transfer-in-cellobiose-dehydrogenase-is-governed-by-surface-electrostatics
#8
Alan Kadek, Daniel Kavan, Julien Marcoux, Johann Stojko, Alfons K G Felice, Sarah Cianférani, Roland Ludwig, Petr Halada, Petr Man
BACKGROUND: Cellobiose dehydrogenase (CDH) is a fungal extracellular oxidoreductase which fuels lytic polysaccharide monooxygenase with electrons during cellulose degradation. Interdomain electron transfer between the flavin and cytochrome domain in CDH, preceding the electron flow to lytic polysaccharide monooxygenase, is known to be pH dependent, but the exact mechanism of this regulation has not been experimentally proven so far. METHODS: To investigate the structural aspects underlying the domain interaction in CDH, hydrogen/deuterium exchange (HDX-MS) with improved proteolytic setup (combination of nepenthesin-1 with rhizopuspepsin), native mass spectrometry with ion mobility and electrostatics calculations were used...
November 13, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27846722/-utilization-of-hydrogen-deuterium-exchange-in-biopharmaceutical-industry
#9
D Coufalová, B Vojtěšek, L Hernychova
BACKGROUND: The development of biopharmaceutics is the fastest growing segment of the present pharmaceutical industry. The analysis of proteins therapeutics is a challenging task due to their large size and complexity of spatial structure. Any changes in the primary, secondary, tertiary or quaternary protein structure can have huge impact on their function, efficiency and toxicity. Mass spectrometry proved itself to be a powerful tool for analysis of primary protein structure (amino acid sequence) and thanks to the development of new techniques in last years it is able to analyse higher order protein structures...
2016: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/27845431/ligand-mediated-changes-in-conformational-dynamics-of-npma-implications-for-ribosomal-interactions
#10
Nilofer Husain, Nikhil Kumar Tulsian, Wang Loo Chien, Sushant Suresh, Ganesh Srinivasan Anand, J Sivaraman
Aminoglycosides are broad-spectrum antibiotics that bind to the 30S ribosomal subunit (30S) of bacteria and disrupt protein translation. NpmA, a structurally well-characterized methyltransferase identified in an E. coli clinical isolate, catalyzes methylation of 30S at A1408 of the 16S rRNA and confers aminoglycoside resistance. Using sucrose cushion centrifugation and isothermal titration calorimetry, we first confirmed the binding between NpmA and 30S. Next, we performed amide Hydrogen/Deuterium Exchange Mass Spectrometry (HDXMS) of apo NpmA and in the presence and absence of SAM/SAH...
November 15, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27807976/a-residue-resolved-bayesian-approach-to-quantitative-interpretation-of-hydrogen-deuterium-exchange-from-mass-spectrometry-application-to-characterizing-protein-ligand-interactions
#11
Daniel John Saltzberg, Howard B Broughton, Riccardo Pellarin, Michael J Chalmers, Alfonso Espada, Jeffrey A Dodge, Bruce D Pascal, Patrick R Griffin, Christine Humblet, Andrej Sali
Characterization of interactions between proteins and other molecules is crucial for understanding the mechanisms of action of biological systems and, thus, drug discovery. An increasingly useful approach to mapping these interactions is measurement of hydrogen/deuterium exchange (HDX) using mass spectrometry (HDX-MS), which measures the time-resolved deuterium incorporation of peptides obtained by enzymatic digestion of the protein. Comparison of exchange rates between apo- and ligand-bound conditions results in a mapping of the differential HDX (ΔHDX) of the ligand...
November 3, 2016: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/27806276/the-ph-dependent-trigger-in-diphtheria-toxin-t-domain-comes-with-a-safety-latch
#12
Mykola V Rodnin, Jing Li, Michael L Gross, Alexey S Ladokhin
Protein-side-chain protonation, coupled to conformational rearrangements, is one way of regulating physiological function caused by changes in protein environment. Specifically, protonation of histidine residues has been implicated in pH-dependent conformational switching in several systems, including the diphtheria toxin translocation (T) domain, which is responsible for the toxin's cellular entry via the endosomal pathway. Our previous studies a) identified protonation of H257 as a major component of the T domain's conformational switch and b) suggested the possibility of a neighboring H223 acting as a modulator, affecting the protonation of H257 and preventing premature conformational changes outside the endosome...
November 1, 2016: Biophysical Journal
https://www.readbyqxmd.com/read/27797822/the-diverse-and-expanding-role-of-mass-spectrometry-in-structural-and-molecular-biology
#13
REVIEW
Philip Lössl, Michiel van de Waterbeemd, Albert Jr Heck
The emergence of proteomics has led to major technological advances in mass spectrometry (MS). These advancements not only benefitted MS-based high-throughput proteomics but also increased the impact of mass spectrometry on the field of structural and molecular biology. Here, we review how state-of-the-art MS methods, including native MS, top-down protein sequencing, cross-linking-MS, and hydrogen-deuterium exchange-MS, nowadays enable the characterization of biomolecular structures, functions, and interactions...
October 26, 2016: EMBO Journal
https://www.readbyqxmd.com/read/27783482/an-asymmetric-antithrombin-dimer-is-a-key-intermediate-for-polymerization-revealed-by-hydrogen-deuterium-exchange-mass-spectrometry
#14
Morten Beck Trelle, Shona H Pedersen, Eva Christina Østerlund, Jeppe Buur Madsen, Søren Risom Kristensen, Thomas J D Jørgensen
Antithrombin deficiency is associated with increased risk of venous thrombosis. In certain families this condition is caused by pathogenic polymerization of mutated antithrombin in the blood. To facilitate future development of pharmaceuticals against antithrombin polymerization an improved understanding of the polymerogenic intermediates is crucial. However, X-ray crystallography of these intermediates is severely hampered by the difficulty in obtaining well-diffracting crystals of transient and heterogeneous noncovalent protein assemblies...
October 26, 2016: Analytical Chemistry
https://www.readbyqxmd.com/read/27751724/structural-dynamics-in-ras-and-related-proteins-upon-nucleotide-switching
#15
Rane A Harrison, Jia Lu, Martin Carrasco, John Hunter, Anuj Manandhar, Sudershan Gondi, Kenneth D Westover, John R Engen
Structural dynamics of Ras proteins contribute to their activity in signal transduction cascades. Directly targeting Ras proteins with small molecules may rely on movement of a conserved structural motif, switch II. To understand Ras signaling and advance Ras targeting strategies, experimental methods to measure Ras dynamics are required. Here we demonstrate the utility of hydrogen-deuterium exchange mass spectrometry to measure Ras dynamics by studying representatives from two branches of the Ras superfamily, Ras and Rho...
October 14, 2016: Journal of Molecular Biology
https://www.readbyqxmd.com/read/27732584/molecular-basis-of-lys11-polyubiquitin-specificity-in-the-deubiquitinase-cezanne
#16
Tycho E T Mevissen, Yogesh Kulathu, Monique P C Mulder, Paul P Geurink, Sarah L Maslen, Malte Gersch, Paul R Elliott, John E Burke, Bianca D M van Tol, Masato Akutsu, Farid El Oualid, Masato Kawasaki, Stefan M V Freund, Huib Ovaa, David Komander
The post-translational modification of proteins with polyubiquitin regulates virtually all aspects of cell biology. Eight distinct chain linkage types co-exist in polyubiquitin and are independently regulated in cells. This 'ubiquitin code' determines the fate of the modified protein. Deubiquitinating enzymes of the ovarian tumour (OTU) family regulate cellular signalling by targeting distinct linkage types within polyubiquitin, and understanding their mechanisms of linkage specificity gives fundamental insights into the ubiquitin system...
October 12, 2016: Nature
https://www.readbyqxmd.com/read/27727023/meaning-and-consequence-of-the-coexistence-of-competitive-hydrogen-bond-salt-forms-on-the-dissociation-orientation-of-non-covalent-complexes
#17
Ekaterina Darii, Sandra Alves, Yves Gimbert, Alain Perret, Jean-Claude Tabet
Non-covalent complexes (NCC) between hexose monophosphates (HexP) and arginine (R) were analyzed using ESI MS and MS/MS in negative mode under different (hard, HC and soft, SC) desolvation conditions. High resolution mass spectrometry (HRMS) revealed the presence of different ionic species, namely, homo- and heteromultimers of R and HexP. Deprotonated heterodimers and corresponding sodiated species were enhanced under HC likely due to a decrease in available charge number associated with the reduction of H(+)/Na(+) exchange...
September 26, 2016: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/27703196/degradation-of-redox-sensitive-proteins-including-peroxiredoxins-and-dj-1-is-promoted-by-oxidation-induced-conformational-changes-and-ubiquitination
#18
In-Kang Song, Jae-Jin Lee, Jin-Hwan Cho, Jihye Jeong, Dong-Hae Shin, Kong-Joo Lee
Reactive oxygen species (ROS) are key molecules regulating various cellular processes. However, what the cellular targets of ROS are and how their functions are regulated is unclear. This study explored the cellular proteomic changes in response to oxidative stress using H2O2 in dose- and recovery time-dependent ways. We found discernible changes in 76 proteins appearing as 103 spots on 2D-PAGE. Of these, Prxs, DJ-1, UCH-L3 and Rla0 are readily oxidized in response to mild H2O2 stress, and then degraded and active proteins are newly synthesized during recovery...
October 5, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27690308/the-cac1-subunit-of-histone-chaperone-caf-1-organizes-caf-1-h3-h4-architecture-and-tetramerizes-histones
#19
Wallace H Liu, Sarah C Roemer, Yeyun Zhou, Zih-Jie Shen, Briana K Dennehey, Jeremy L Balsbaugh, Jennifer C Liddle, Travis Nemkov, Natalie G Ahn, Kirk C Hansen, Jessica K Tyler, Mair Ea Churchill
The histone chaperone Chromatin Assembly Factor 1 (CAF-1) deposits tetrameric (H3/H4)2 histones onto newly-synthesized DNA during DNA replication. To understand the mechanism of the tri-subunit CAF-1 complex in this process, we investigated the protein-protein interactions within the CAF-1-H3/H4 architecture using biophysical and biochemical approaches. Hydrogen/deuterium exchange and chemical cross-linking coupled to mass spectrometry reveal interactions that are essential for CAF-1 function in budding yeast, and importantly indicate that the Cac1 subunit functions as a scaffold within the CAF-1-H3/H4 complex...
September 30, 2016: ELife
https://www.readbyqxmd.com/read/27689696/high-resolution-mapping-of-bactericidal-monoclonal-antibody-binding-epitopes-on-staphylococcus-aureus-antigen-mntc
#20
Alexey V Gribenko, Kevin Parris, Lidia Mosyak, Sheng Li, Luke Handke, Julio C Hawkins, Elena Severina, Yury V Matsuka, Annaliesa S Anderson
The Staphylococcus aureus manganese transporter protein MntC is under investigation as a component of a prophylactic S.aureus vaccine. Passive immunization with monoclonal antibodies mAB 305-78-7 and mAB 305-101-8 produced using MntC was shown to significantly reduce S. aureus burden in an infant rat model of infection. Earlier interference mapping suggested that a total of 23 monoclonal antibodies generated against MntC could be subdivided into three interference groups, representing three independent immunogenic regions...
September 2016: PLoS Pathogens
keyword
keyword
61452
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"