keyword
MENU ▼
Read by QxMD icon Read
search

Hydrogen exchange mass spectrometry

keyword
https://www.readbyqxmd.com/read/28533135/enhanced-local-disorder-in-a-clinically-elusive-von-willebrand-factor-provokes-high-affinity-platelet-clumping
#1
Alexander Tischer, Venkata R Machha, Juan P Frontroth, Maria A Brehm, Tobias Obser, Reinhard Schneppenheim, Leland Mayne, S Walter Englander, Matthew Auton
Mutation of the cysteines forming the disulfide loop of the platelet GPIbα adhesive A1 domain of von Willebrand factor causes quantitative VWF deficiencies in the blood and von Willebrand disease. We report two cases of transient severe thrombocytopenia induced by DDAVP-treatment. Cys1272Trp and Cys1458Tyr mutations identified by genetic sequencing implicate an abnormal gain-of-function phenotype, evidenced by thrombocytopenia, that quickly relapses back to normal platelet counts and deficient plasma VWF. Using surface plasmon resonance, analytical rheology, and hydrogen-deuterium exchange mass spectrometry (HXMS), we decipher mechanisms of A1-GPIbα mediated platelet adhesion and resolve dynamic secondary structure elements that regulate the binding pathway...
May 19, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28515318/molecular-mechanism-of-activation-of-class-ia-phosphoinositide-3-kinases-pi3ks-by-membrane-localized-hras
#2
Braden D Siempelkamp, Manoj K Rathinaswamy, Meredith L Jenkins, John E Burke
Class IA PI3Ks are involved in the generation of the key lipid signaling molecule phosphatidylinositol 3,4,5-trisphosphate (PIP3), and inappropriate activation of this pathway is implicated in a multitude of human diseases, including cancer, inflammation, and primary immunodeficiencies. Class IA PI3Ks are activated downstream of the Ras superfamily of GTPases, and Ras-PI3K interaction plays a key role in promoting tumor formation and maintenance in Ras-driven tumors. Investigating the detailed molecular events in the Ras-PI3K interaction has been challenging because it occurs on a membrane surface...
May 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28505408/ion-mobility-hydrogen-deuterium-exchange-and-isotope-scrambling-tools-to-aid-compound-identification-in-omics-mixtures
#3
Hossein Maleki, Megan M Maurer, Nima Ronaghi, Stephen J Valentine
Liquid chromatography tandem mass spectrometry (LC-MS/MS), a widely used method for comparative 'omics analysis, experiences challenges with compound identification due to matrix effects, difficulty in separating isomer and isobaric ions, and long analysis times. Ion mobility spectrometry (IMS) has proven to be useful in separating isomer and isobar ions, however IMS-MS suffers from decreased peak capacity duet to the correlation in ion size and mass. In proof-of-principle experiments, the use of gas-phase hydrogen/deuterium exchange (HDX) combined with IMS-MS/MS techniques is demonstrated to offer advantages for compound identification...
May 15, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28504253/dynamic-diversity-of-synthetic-supramolecular-polymers-in-water-as-revealed-by-hydrogen-deuterium-exchange
#4
Xianwen Lou, René P M Lafleur, Christianus M A Leenders, Sandra M C Schoenmakers, Nicholas M Matsumoto, Matthew B Baker, Joost L J van Dongen, Anja R A Palmans, E W Meijer
Numerous self-assembling molecules have been synthesized aiming at mimicking both the structural and dynamic properties found in living systems. Here we show the application of hydrogen/deuterium exchange (HDX) mass spectrometry (MS) to unravel the nanoscale organization and the structural dynamics of synthetic supramolecular polymers in water. We select benzene-1,3,5-tricarboxamide (BTA) derivatives that self-assemble in H2O to illustrate the strength of this technique for supramolecular polymers. The BTA structure has six exchangeable hydrogen atoms and we follow their exchange as a function of time after diluting the H2O solution with a 100-fold excess of D2O...
May 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28497950/deamidation-slows-curli-amyloid-protein-aggregation
#5
Hanliu Wang, Qin Shu, Carl Frieden, Michael L Gross
Non-enzymatic deamidation of asparagine and glutamine in peptides and proteins is a frequent modification both in vivo and in vitro. The biological effect is not completely understood, but it is often associated with protein degradation and loss of biological function. Here we describe the deamidation of CsgA, the major protein subunit of curli, which are important proteinaceous components of biofilms. CsgA has a high content of Asn and Gln, a feature seen in other proteins that self-aggregate. We have implemented an approach to monitor deamidation rapidly by following the globally centroid mass shift, providing guidance for studies at the residue level...
May 12, 2017: Biochemistry
https://www.readbyqxmd.com/read/28490633/single-particle-electron-microscopy-structure-of-udp-glucose-glycoprotein-glucosyltransferase-suggests-a-selectivity-mechanism-for-misfolded-proteins
#6
Daniel Calles-Garcia, Meng Yang, Naoto Soya, Roberto Melero, Marie Ménade, Yukishige Ito, Javier Vargas, Gergely L Lukacs, Justin M Kollman, Guennadi Kozlov, Kalle Gehring
The enzyme UDP-glucose:glycoprotein glucosyltransferase (UGGT) mediates quality control of glycoproteins in the endoplasmic reticulum by attaching glucose to N-linked glycan of misfolded proteins. As a sensor, UGGT ensures that misfolded proteins are recognized by the lectin chaperones and do not leave the secretory pathway. The structure of UGGT and the mechanism of its selectivity for misfolded proteins have been unknown for 25 years. Here, we used negative-stain electron microscopy and small-angle X-ray scattering to determine the structure of UGGT from Drosophila melanogaster at 18 Å resolution...
May 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28488200/application-of-atmospheric-pressure-photoionization-h-d-exchange-mass-spectrometry-for-speciation-of-sulfur-containing-compounds
#7
Thamina Acter, Donghwi Kim, Arif Ahmed, Ji-Hyoung Ha, Sunghwan Kim
Herein we report the observation of atmospheric pressure in-source hydrogen-deuterium exchange (HDX) of thiol group for the first time. The HDX for thiol group was optimized for positive atmospheric pressure photoionization (APPI) mass spectrometry (MS). The optimized HDX-MS was applied for 31 model compounds (thiols, thiophenes, and sulfides) to demonstrate that exchanged peaks were observed only for thiols. The optimized method has been successfully applied to the isolated fractions of sulfur-rich oil samples...
May 9, 2017: Journal of the American Society for Mass Spectrometry
https://www.readbyqxmd.com/read/28481522/rapid-hydrogen-deuterium-exchange-in-liquid-droplets
#8
Erik T Jansson, Yin-Hung Lai, Juan G Santiago, Richard N Zare
The rate of hydrogen-deuterium exchange (HDX) in aqueous droplets of phenethylamine has been determined with submillisecond temporal resolution by mass spectrometry using nanoelectrospray ionization with a theta-capillary. The average speed of the microdroplets is measured using microparticle image velocimetry. The droplet travel time is varied from 20 to 320 μs by changing the distance between the emitter and the heated inlet to the mass spectrometer and the voltage applied to the emitter source. The droplets were found to accelerate by ∼30% during their observable travel time...
May 12, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28481113/hydrogen-deuterium-exchange-mass-spectrometry-reveals-mechanistic-details-of-activation-of-nucleoside-diphosphate-kinases-by-oligomerization
#9
Alain Dautant, Philippe Meyer, Florian Georgescauld
Most oligomeric proteins become active only after assembly, but why oligomerization is required to support function is not well understood. Here, we address this question using the wild type (WT) and a destabilized mutant (D93N) of the hexameric nucleoside diphosphate kinase from the pathogen Mycobacterium tuberculosis (Mt-NDPK). The conformational dynamics and oligomeric states of each were analyzed during unfolding and/or folding by hydrogen/deuterium exchange mass spectrometry (HDX-MS) at peptide resolution and by additional biochemical techniques...
May 17, 2017: Biochemistry
https://www.readbyqxmd.com/read/28481111/conformational-changes-in-active-and-inactive-states-of-human-pp2c%C3%AE-characterized-by-hydrogen-deuterium-exchange-mass-spectrometry
#10
Sharlyn J Mazur, Elyssia S Gallagher, Subrata Debnath, Stewart R Durell, Kyle W Anderson, Lisa M Miller Jenkins, Ettore Appella, Jeffrey W Hudgens
PPM serine/threonine protein phosphatases function in signaling pathways and require millimolar concentrations of Mn(2+) or Mg(2+) ions for activity. Whereas the crystal structure of human PP2Cα displayed two tightly bound Mn(2+) ions in the active site, recent investigations of PPM phosphatases have characterized the binding of a third, catalytically essential metal ion. The binding of the third Mg(2+) to PP2Cα was reported to have millimolar affinity and to be entropically driven, suggesting it may be structurally and catalytically important...
May 12, 2017: Biochemistry
https://www.readbyqxmd.com/read/28474266/gas-phase-intercluster-thiyl-radical-induced-c-h-bond-homolysis-selectively-forms-sugar-c2-radical-cations-of-methyl-d-glucopyranoside-isotopic-labeling-studies-and-cleavage-reactions
#11
Sandra Osburn, Gaetano Speciale, Spencer J Williams, Richard A J O'Hair
A suite of isotopologues of methyl D-glucopyranosides is used in conjunction with multistage mass spectrometry experiments to determine the radical site and cleavage reactions of sugar radical cations formed via a recently developed 'bio-inspired' method. In the first stage of CID (MS(2)), collision-induced dissociation (CID) of a protonated noncovalent complex between the sugar and S-nitrosocysteamine, [H3NCH2CH2SNO + M](+), unleashes a thiyl radical via bond homolysis to give the noncovalent radical cation, [H3NCH2CH2S(•) + M](+)...
May 4, 2017: Journal of the American Society for Mass Spectrometry
https://www.readbyqxmd.com/read/28465180/application-of-isotope-exchange-based-mass-spectrometry-to-understand-the-mechanism-of-inhibition-of-sickle-hemoglobin-polymerization-upon-oxygenation
#12
Rajdeep Das, Amrita Mitra, Vijay Bhat, Amit Kumar Mandal
Sickle hemoglobin (HbS) polymerization initiates in the deoxy state with the binding of hydrophobic patch formed by the isopropyl group of βVal6 residue of a hemoglobin tetramer with the hydrophobic pocket of another tetramer, whose hydrophobic patch binds to the hydrophobic groove of a third molecule. Subsequent elongation of a single stranded polymer followed by the formation of a double strand and finally combination of seven such pairs of double strands results in a fourteen stranded fibrous polymer. Precipitation of this fiber inside the erythrocytes results in sickling of red blood cells...
April 29, 2017: Journal of Structural Biology
https://www.readbyqxmd.com/read/28448048/time-resolved-electrospray-ionization-hydrogen-deuterium-exchange-mass-spectrometry-for-studying-protein-structure-and-dynamics
#13
Cristina Lento, Shaolong Zhu, Kerene A Brown, Ruth Knox, Peter Liuni, Derek J Wilson
Intrinsically disordered proteins (IDPs) have long been a challenge to structural biologists due to their lack of stable secondary structure elements. Hydrogen-Deuterium Exchange (HDX) measured at rapid time scales is uniquely suited to detect structures and hydrogen bonding networks that are briefly populated, allowing for the characterization of transient conformers in native ensembles. Coupling of HDX to mass spectrometry offers several key advantages, including high sensitivity, low sample consumption and no restriction on protein size...
April 17, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28442430/design-and-purification-of-active-truncated-phosphoinositide-3-kinase-gamma-protein-constructs-for-structural-studies
#14
A Vujičić Žagar, L Scapozza, O Vadas
Phosphoinositide 3-kinase gamma (PI3Kγ) is a lipid kinase that plays a crucial role in cell migration, chemotaxis, oxidative burst and myocardial contractility. It is activated downstream of G protein-coupled receptors (GPCRs) and small GTPases of Ras superfamily. PI3Kγ is a heterodimer composed of a catalytic and a regulatory subunit that is expressed mostly in hematopoietic cells and in the heart. Although it has attracted a lot of attention because of its link with tumor inflammation and heart diseases, its regulation is still not fully understood...
April 22, 2017: Protein Expression and Purification
https://www.readbyqxmd.com/read/28441028/application-of-gc-ms-soft-ionization-for-isomeric-biological-compound-analysis
#15
Takeshi Furuhashi, Koji Okuda
Isomers are compounds with the same molecular formula. Many different types of isomers are ubiquitous and play important roles in living organisms. Despite their early discovery, the actual analysis of isomers has been tricky and has confounded researchers. Using mass spectrometry (MS) to distinguish or identify isomers is an emergent topic and challenge for analytical chemists. We review some techniques for analyzing isomers with emphasis on MS, e.g., the roles of ion reaction, hydrogen-deuterium exchange, ion mobility mass spectrometry, ion spectroscopy and energy change in producing isomer-specific fragments...
April 25, 2017: Critical Reviews in Analytical Chemistry
https://www.readbyqxmd.com/read/28440616/discovery-and-characterization-of-a-eukaryotic-initiation-factor-4a-3-selective-inhibitor-that-suppresses-nonsense-mediated-mrna-decay
#16
Misa Iwatani-Yoshihara, Masahiro Ito, Yoshihiro Ishibashi, Hideyuki Oki, Toshio Tanaka, Daisuke Morishita, Takashi Ito, Hiromichi Kimura, Yasuhiro Imaeda, Samuel Aparicio, Atsushi Nakanishi, Tomohiro Kawamoto
Eukaryotic initiation factor 4A-3 (eIF4A3) is an Asp-Glu-Ala-Asp (DEAD) box-family adenosine triphosphate (ATP)-dependent RNA helicase. Subtypes eIF4A1 and eIF4A2 are required for translation initiation, but eIF4A3 participates in the exon junction complex (EJC) and functions in RNA metabolism including nonsense-mediated RNA decay (NMD). No small molecules for NMD inhibition via selective inhibition of eIF4A3 have been discovered. Here, we identified allosteric eIF4A3 inhibitors from a high-throughput screening campaign...
May 10, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28431242/structural-and-functional-analysis-of-a-%C3%AE-2-adrenergic-receptor-complex-with-grk5
#17
Konstantin E Komolov, Yang Du, Nguyen Minh Duc, Robin M Betz, João P G L M Rodrigues, Ryan D Leib, Dhabaleswar Patra, Georgios Skiniotis, Christopher M Adams, Ron O Dror, Ka Young Chung, Brian K Kobilka, Jeffrey L Benovic
The phosphorylation of agonist-occupied G-protein-coupled receptors (GPCRs) by GPCR kinases (GRKs) functions to turn off G-protein signaling and turn on arrestin-mediated signaling. While a structural understanding of GPCR/G-protein and GPCR/arrestin complexes has emerged in recent years, the molecular architecture of a GPCR/GRK complex remains poorly defined. We used a comprehensive integrated approach of cross-linking, hydrogen-deuterium exchange mass spectrometry (MS), electron microscopy, mutagenesis, molecular dynamics simulations, and computational docking to analyze GRK5 interaction with the β2-adrenergic receptor (β2AR)...
April 20, 2017: Cell
https://www.readbyqxmd.com/read/28430446/piecing-together-the-allosteric-patterns-of-chaperonin-groel
#18
Jin Chen, Qian Zhang, Weitong Ren, Wenfei Li
Despite considerable efforts, elucidating the allostery of large macromolecular assemblies at a molecular level in solution remains technically challenging due to its structural complexity. Here we have employed an approach combining amide backbone hydrogen/deuterium exchange coupled with mass spectrometry, fluorescence spectroscopy, and molecular simulations to characterize allosteric patterns of chaperonin GroEL, an ∼800 kDa tetradecamer from E. coli. Using available crystal structures of GroEL, we quantitatively map out GroEL allosteric changes in solution by resolving exchange behaviors of 133 overlapping proteolytic peptides with more than 95% sequence coverage...
May 4, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28428550/structure-based-dynamic-arrays-in-regulatory-domains-of-sodium-calcium-exchanger-ncx-isoforms
#19
Moshe Giladi, Su Youn Lee, Yarden Ariely, Yotam Teldan, Rotem Granit, Roi Strulovich, Yoni Haitin, Ka Young Chung, Daniel Khananshvili
Mammalian Na(+)/Ca(2+) exchangers, NCX1 and NCX3, generate splice variants, whereas NCX2 does not. The CBD1 and CBD2 domains form a regulatory tandem (CBD12), where Ca(2+) binding to CBD1 activates and Ca(2+) binding to CBD2 (bearing the splicing segment) alleviates the Na(+)-induced inactivation. Here, the NCX2-CBD12, NCX3-CBD12-B, and NCX3-CBD12-AC proteins were analyzed by small-angle X-ray scattering (SAXS) and hydrogen-deuterium exchange mass-spectrometry (HDX-MS) to resolve regulatory variances in the NCX2 and NCX3 variants...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28426082/deciphering-of-interactions-between-platinated-dna-and-hmgb1-by-hydrogen-deuterium-exchange-mass-spectrometry
#20
Yuanyuan Wang, Zhifeng Du, Wei Zheng, Kui Wu, Decheng Xu, Qun Luo, Yao Zhao, Juanjuan Han, Yangzhong Liu, Fuyi Wang
A high mobility group box 1 (HMGB1) protein has been reported to recognize both 1,2-intrastrand crosslinked DNA by cisplatin (1,2-cis-Pt-DNA) and monofunctional platinated DNA using trans-[PtCl2(NH3)(thiazole)] (1-trans-PtTz-DNA). However, the molecular basis of recognition between the trans-PtTz-DNA and HMGB1 remains unclear. In the present work, we described a hydrogen/deuterium exchange mass spectrometry (HDX-MS) method in combination with docking simulation to decipher the interactions of platinated DNA with domain A of HMGB1...
May 16, 2017: Dalton Transactions: An International Journal of Inorganic 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"