keyword
MENU ▼
Read by QxMD icon Read
search

Hydrogen exchange mass spectrometry

keyword
https://www.readbyqxmd.com/read/28096372/helical-structure-stability-and-dynamics-in-human-apolipoprotein-e3-and-e4-by-hydrogen-exchange-and-mass-spectrometry
#1
Palaniappan S Chetty, Leland Mayne, Sissel Lund-Katz, S Walter Englander, Michael C Phillips
Apolipoprotein E (apoE) plays a critical role in cholesterol transport in both peripheral circulation and brain. Human apoE is a polymorphic 299-residue protein in which the less common E4 isoform differs from the major E3 isoform only by a C112R substitution. ApoE4 interacts with lipoprotein particles and with the amyloid-β peptide, and it is associated with increased incidence of cardiovascular and Alzheimer's disease. To understand the structural basis for the differences between apoE3 and E4 functionality, we used hydrogen-deuterium exchange coupled with a fragment separation method and mass spectrometric analysis to compare their secondary structures at near amino acid resolution...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28077807/folding-of-apomyoglobin-analysis-of-transient-intermediate-structure-during-refolding-using-quick-hydrogen-deuterium-exchange-and-nmr
#2
Chiaki Nishimura
The structures of apomyoglobin folding intermediates have been widely analyzed using physical chemistry methods including fluorescence, circular dichroism, small angle X-ray scattering, NMR, mass spectrometry, and rapid mixing. So far, at least two intermediates (on sub-millisecond- and millisecond-scales) have been demonstrated for apomyoglobin folding. The combination of pH-pulse labeling and NMR is a useful tool for analyzing the kinetic intermediates at the atomic level. Its use has revealed that the latter-phase kinetic intermediate of apomyoglobin (6 ms) was composed of helices A, B, G and H, whereas the equilibrium intermediate, called the pH 4 molten-globule intermediate, was composed mainly of helices A, G and H...
2017: Proceedings of the Japan Academy. Series B, Physical and Biological Sciences
https://www.readbyqxmd.com/read/28063489/using-hydrogen-deuterium-exchange-mass-spectrometry-to-examine-protein-membrane-interactions
#3
O Vadas, M L Jenkins, G L Dornan, J E Burke
Many fundamental cellular processes are controlled via assembly of a network of proteins at membrane surfaces. The proper recruitment of proteins to membranes can be controlled by a wide variety of mechanisms, including protein lipidation, protein-protein interactions, posttranslational modifications, and binding to specific lipid species present in membranes. There are, however, only a limited number of analytical techniques that can study the assembly of protein-membrane complexes at the molecular level. A relatively new addition to the set of techniques available to study these protein-membrane systems is the use of hydrogen-deuterium exchange mass spectrometry (HDX-MS)...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28063488/analyses-of-calcium-independent-phospholipase-a2beta-ipla2%C3%AE-in-biological-systems
#4
S E Barbour, S Ramanadham
The Ca(2+)-independent phospholipases A2 (iPLA2s) are part of a diverse family of PLA2s, manifest activity in the absence of Ca(2+), are ubiquitous, and participate in a variety of biological processes. Among the iPLA2s, the cytosolic iPLA2β has received considerable attention and ongoing studies from various laboratories suggest that dysregulation of iPLA2β can have a profound impact on the onset and/or progression of many diseases (e.g., cardiovascular, neurological, metabolic, autoimmune). Therefore, appropriate approaches are warranted to gain a better understanding of the role of iPLA2β in vivo and its contribution to pathophysiology...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28062800/novel-allosteric-pathway-of-eg5-regulation-identified-through-multivariate-statistical-analysis-of-hx-ms-ligand-screening-data
#5
Joey G Sheff, Farshad Farshidfar, Oliver F Bathe, Karen Kopciuk, Francesco Gentile, Jack Tuszynski, Khaled Barakat, David C Schriemer
The mitotic kinesin Eg5 is an important target in cancer chemotherapy. A structurally diverse collection of canonical loop L5 inhibitors engage an allosteric pathway that includes elements of its microtubule binding region. However, recent evidence suggests that Eg5 may permit alternative allosteric mechanisms. Terpendole E, a natural-product Eg5 inhibitor, is active against mutants resistant to canonical loop L5 inhibitors and appears to offer a unique mode of inhibition. To investigate the variety of inhibitor responses, the structure-function properties of eighteen kinesin inhibitors were quantified with hydrogen-exchange mass spectrometry (HX-MS), functional analysis and molecular modeling...
January 5, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28062799/a-two-pronged-binding-mechanism-of-igg-to-the-neonatal-fc-receptor-controls-complex-stability-and-igg-serum-half-life
#6
Pernille Foged Jensen, Angela Schoch, Vincent Larraillet, Maximiliane Hilger, Tilman Schlothauer, Thomas Emrich, Kasper Dyrbert Rand
The success of recombinant monoclonal immunoglobulins (IgG) is rooted in their ability to target distinct antigens with high affinity combined with an extraordinarily long serum half-life, typically around three weeks. The pharmacokinetics of IgGs is intimately linked to the recycling mechanism of the neonatal Fc receptor (FcRn). For long serum half-life of therapeutic IgGs, the highly pH dependent interaction with FcRn needs to be balanced to allow efficient FcRn binding and release at slightly acidic pH and physiological pH, respectively...
January 6, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28032989/how-does-your-protein-fold-elucidating-the-apomyoglobin-folding-pathway
#7
H Jane Dyson, Peter E Wright
Although each type of protein fold and in some cases individual proteins within a fold classification can have very different mechanisms of folding, the underlying biophysical and biochemical principles that operate to cause a linear polypeptide chain to fold into a globular structure must be the same. In an aqueous solution, the protein takes up the thermodynamically most stable structure, but the pathway along which the polypeptide proceeds in order to reach that structure is a function of the amino acid sequence, which must be the final determining factor, not only in shaping the final folded structure, but in dictating the folding pathway...
January 17, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28026060/alkene-metalates-as-hydrogenation-catalysts
#8
Philipp Büschelberger, Dominik Gärtner, Efrain Reyes-Rodriguez, Friedrich Kreyenschmidt, Konrad Koszinowski, Axel Jacobi von Wangelin, Robert Wolf
First-row transition metal complexes hold great potential as catalysts for hydrogenations and related reductive reactions. Homoleptic and heteroleptic arene/alkene metalates(1-) (M = Co, Fe) are a structurally distinct catalyst class with good activities in hydrogenations of alkenes and alkynes. The first syntheses of the heteroleptic cobaltates [K([18crown-6])][Co(cod)(styrene)2] (5), [K([18]crown-6)][Co(dct)(cod)] (6), and the homoleptic complex [K(thf)2][Co(dct)2] (7, dct = dibenzo[a,e]cyclooctatetraene, cod = 1,5 cyclooctadiene) are reported...
December 27, 2016: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28024318/an-empirical-method-to-accurately-determine-peptide-averaged-protection-factors-from-hydrogen-exchange-ms-data
#9
Benjamin Thomas Walters
Amide hydrogen exchange experiments measured by mass spectrometry have become commonplace to study protein structural dynamics; however, the underdetermined nature of these measurements render extraction of exchange rates unreliable at the level of individual peptides. This prevents orthogonal verification of results and severely limits interpretation of the data. This work describes an easy-to-implement empirical method to determine the change in an observed rate constant or the average change in multiple rate constants as compared to some reference condition...
December 19, 2016: Analytical Chemistry
https://www.readbyqxmd.com/read/28024262/levothyroxine-sodium-revisited-a-wholistic-structural-elucidation-approach-of-new-impurities-via-hplc-hrms-ms-on-line-h-d-exchange-nmr-spectroscopy-and-chemical-synthesis
#10
M Ruggenthaler, J Grass, W Schuh, C G Huber, R J Reischl
The structural elucidation of unknown pharmaceutical impurities plays an important role in the quality control of newly developed and well-established active pharmaceutical ingredients (APIs). The United States Pharmacopeia (USP) monograph for the API Levothyroxine Sodium, a synthetic thyroid hormone, features two high pressure liquid chromatography (HPLC) methods using UV-VIS absorption detection to determine organic impurities in the drug substance. The impurity profile of the first USP method ("Procedure 1") has already been extensively studied, however for the second method ("Procedure 2"), which exhibits a significantly different impurity profile, no wholistic structural elucidation of impurities has been performed yet...
December 14, 2016: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28008853/ric-8a-a-g-protein-chaperone-with-nucleotide-exchange-activity-induces-long-range-secondary-structure-changes-in-g%C3%AE
#11
Ravi Kant, Baisen Zeng, Celestine J Thomas, Brian Bothner, Stephen R Sprang
Cytosolic Ric-8A has guanine nucleotide exchange factor (GEF) activity and is a chaperone for several classes of heterotrimeric G protein α subunits in vertebrates. Using Hydrogen-Deuterium Exchange-Mass Spectrometry (HDX-MS) we show that Ric-8A disrupts the secondary structure of the Gα Ras-like domain that girds the guanine nucleotide-binding site, and destabilizes the interface between the Gαi1 Ras and helical domains, allowing domain separation and nucleotide release. These changes are largely reversed upon binding GTP and dissociation of Ric-8A...
December 23, 2016: ELife
https://www.readbyqxmd.com/read/28000716/%C3%AE-subunit-myristoylation-functions-as-an-energy-sensor-by-modulating-the-dynamics-of-amp-activated-protein-kinase
#12
Nada Ali, Naomi Ling, Srinath Krishnamurthy, Jonathan S Oakhill, John W Scott, David I Stapleton, Bruce E Kemp, Ganesh Srinivasan Anand, Paul R Gooley
The heterotrimeric AMP-activated protein kinase (AMPK), consisting of α, β and γ subunits, is a stress-sensing enzyme that is activated by phosphorylation of its activation loop in response to increases in cellular AMP. N-terminal myristoylation of the β-subunit has been shown to suppress Thr172 phosphorylation, keeping AMPK in an inactive state. Here we use amide hydrogen-deuterium exchange mass spectrometry (HDX-MS) to investigate the structural and dynamic properties of the mammalian myristoylated and non-myristoylated inactivated AMPK (D139A) in the presence and absence of nucleotides...
December 21, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27998708/conformations-of-jnk3%C3%AE-splice-variants-analyzed-by-hydrogen-deuterium-exchange-mass-spectrometry
#13
Ji Young Park, Youngjoo Yun, Ka Young Chung
c-Jun N-terminal kinases (JNKs) are members of the mitogen-activated protein kinase (MAPK) family that regulate apoptosis, inflammation, cytokine production, and metabolism. MAPKs undergo various splicing within their kinase domains. Unlike other MAPKs, JNKs have alternative splicing at the C-terminus, resulting in long and short variants. Functional or conformational effects due to the elongated C-terminal tail in the long splice variants have not been investigated nor has the conformation of the C-terminal tail been analyzed...
December 18, 2016: Journal of Structural Biology
https://www.readbyqxmd.com/read/27995962/engineering-the-surface-properties-of-a-human-monoclonal-antibody-prevents-self-association-and-rapid-clearance-in-vivo
#14
Claire L Dobson, Paul W A Devine, Jonathan J Phillips, Daniel R Higazi, Christopher Lloyd, Bojana Popovic, Joanne Arnold, Andrew Buchanan, Arthur Lewis, Joanne Goodman, Christopher F van der Walle, Peter Thornton, Lisa Vinall, David Lowne, Anna Aagaard, Lise-Lotte Olsson, Anna Ridderstad Wollberg, Fraser Welsh, Theodoros K Karamanos, Clare L Pashley, Matthew G Iadanza, Neil A Ranson, Alison E Ashcroft, Alistair D Kippen, Tristan J Vaughan, Sheena E Radford, David C Lowe
Uncontrolled self-association is a major challenge in the exploitation of proteins as therapeutics. Here we describe the development of a structural proteomics approach to identify the amino acids responsible for aberrant self-association of monoclonal antibodies and the design of a variant with reduced aggregation and increased serum persistence in vivo. We show that the human monoclonal antibody, MEDI1912, selected against nerve growth factor binds with picomolar affinity, but undergoes reversible self-association and has a poor pharmacokinetic profile in both rat and cynomolgus monkeys...
December 20, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27992649/kinetic-isotope-effects-and-hydrogen-deuterium-exchange-reveal-large-conformational-changes-during-the-catalysis-of-the-clostridium-acetobutylicum-spore-photoproduct-lyase
#15
Linlin Yang, Jagat Adhikari, Michael L Gross, Lei Li
Spore photoproduct lyase (SPL) catalyzes the direct reversal of a thymine dimer 5-thyminyl-5,6-dihydrothymine (i.e., the spore photoproduct (SP)) to two thymine residues in germinating endospores. Previous studies suggest that SPL from the bacterium Bacillus subtilis (Bs) harbors an unprecedented radical transfer pathway starting with cysteine 141 proceeding through tyrosine 99. However, in SPL from the bacterium C. acetobutylicum (Ca), the cysteine (at position 74) and tyrosine are located on the opposite sides of a substrate binding pocket that has to collapse to bring the two residues into proximity, enabling the C→Y radical passage as implied in SPL(Bs) ...
December 19, 2016: Photochemistry and Photobiology
https://www.readbyqxmd.com/read/27989622/the-molecular-basis-of-aichi-virus-3a-protein-activation-of-phosphatidylinositol-4-kinase-iii%C3%AE-pi4kb-through-acbd3
#16
Jacob A McPhail, Erik H Ottosen, Meredith L Jenkins, John E Burke
Phosphatidylinositol 4-kinase III beta (PI4KIIIβ) is an essential enzyme in mediating membrane transport, and plays key roles in facilitating viral infection. Many pathogenic positive-sense single-stranded RNA viruses activate PI4KIIIβ to generate phosphatidylinositol 4-phosphate (PI4P)-enriched organelles for viral replication. The molecular basis for PI4KIIIβ activation during viral infection has remained largely unclear. We describe the biochemical reconstitution and characterization of the complex of PI4KIIIβ with the Golgi protein Acyl-coenzyme A binding domain containing protein 3 (ACBD3) and Aichi virus 3A protein on membranes...
December 7, 2016: Structure
https://www.readbyqxmd.com/read/27986851/activation-mode-of-the-eukaryotic-m2g10-trna-methyltransferase-trm11-by-its-partner-protein-trm112
#17
Gabrielle Bourgeois, Julien Marcoux, Jean-Michel Saliou, Sarah Cianférani, Marc Graille
Post-transcriptional and post-translational modifications of factors involved in translation are very important for the control and accuracy of protein biosynthesis. Among these factors, tRNAs harbor the largest variety of grafted chemical structures, which participate in tRNA stability or mRNA decoding. Here, we focused on Trm112 protein, which associates with four different eukaryotic methyltransferases modifying tRNAs (Trm9 and Trm11) but also 18S-rRNA (Bud23) and translation termination factor eRF1 (Mtq2)...
December 15, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27975228/protein-structural-analysis-via-mass-spectrometry-based-proteomics
#18
Antonio Artigues, Owen W Nadeau, Mary Ashley Rimmer, Maria T Villar, Xiuxia Du, Aron W Fenton, Gerald M Carlson
Modern mass spectrometry (MS) technologies have provided a versatile platform that can be combined with a large number of techniques to analyze protein structure and dynamics. These techniques include the three detailed in this chapter: (1) hydrogen/deuterium exchange (HDX), (2) limited proteolysis, and (3) chemical crosslinking (CX). HDX relies on the change in mass of a protein upon its dilution into deuterated buffer, which results in varied deuterium content within its backbone amides. Structural information on surface exposed, flexible or disordered linker regions of proteins can be achieved through limited proteolysis, using a variety of proteases and only small extents of digestion...
2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27943124/probing-the-gaseous-structure-of-a-%C3%AE-hairpin-peptide-with-h-d-exchange-and-electron-capture-dissociation
#19
Rita N Straus, Rebecca A Jockusch
An improved understanding of the extent to which native protein structure is retained upon transfer to the gas phase promises to enhance biological mass spectrometry, potentially streamlining workflows and providing fundamental insights into hydration effects. Here, we investigate the gaseous conformation of a model β-hairpin peptide using gas-phase hydrogen-deuterium (H/D) exchange with subsequent electron capture dissociation (ECD). Global gas-phase H/D exchange levels, and residue-specific exchange levels derived from ECD data, are compared among the wild type 16-residue peptide GB1p and several variants...
December 9, 2016: Journal of the American Society for Mass Spectrometry
https://www.readbyqxmd.com/read/27936623/automated-strong-cation-exchange-cleanup-to-remove-macromolecular-crowding-agents-for-protein-hydrogen-exchange-mass-spectrometry
#20
Farai I Rusinga, David D Weis
Measuring amide hydrogen exchange (HX) of intrinsically disordered proteins (IDPs) in solutions containing high concentrations of macromolecular crowding agents would give new insights into the structure and dynamics of these proteins under crowded conditions. High concentrations of artificial crowders, required to simulate cellular crowding, introduce overwhelming interferences to mass spectrometry (MS) analysis. We have developed a fully automated, dual-stage online cleanup that uses strong cation-exchange (SCX) followed by reversed-phase desalting to remove Ficoll, a synthetic polymer, for HX-MS analysis of proteins under crowded conditions...
December 23, 2016: Analytical Chemistry
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"