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Full-Text Articles in Life Sciences
Concerted Ho2 Elimination From Alpha-Aminoalkylperoxyl Free Radicals: Experimental And Theoretical Evidence From The Gas-Phase Nh2 Chco2 - + O2 Reaction, Gabriel Da Silva, Benjamin Kirk, Celli Lloyd, Adam Trevitt, Stephen Blanksby
Concerted Ho2 Elimination From Alpha-Aminoalkylperoxyl Free Radicals: Experimental And Theoretical Evidence From The Gas-Phase Nh2 Chco2 - + O2 Reaction, Gabriel Da Silva, Benjamin Kirk, Celli Lloyd, Adam Trevitt, Stephen Blanksby
Adam Trevitt
We have investigated the gas-phase reaction of the α- aminoacetate (glycyl) radical anion (NH2 •CHCO2−) with O2 using ion trap mass spectrometry, quantum chemistry, and statistical reaction rate theory. This radical is found to undergo a remarkably rapid reaction with O2 to form the hydroperoxyl radical (HO2 •) and an even-electron imine (NHCHCO2−), with experiments and master equation simulations revealing that reaction proceeds at the ion−molecule collision rate. This reaction is facilitated by a low-energy concerted HO2 • elimination mechanism in the NH2CH(OO•)CO2− peroxyl radical. These findings can explain the widely observed free-radical-mediated oxidation of simple amino acids to amides …
Solution Structure Of Domains Iva And V Of The Tau Subunit Of Escherichia Coli Dna Polymerase Iii And Interaction With The Alpha Subunit, Xun-Cheng Su, Slobodan Jergic, Max A Keniry, Nicholas E. Dixon, Gottfried Otting
Solution Structure Of Domains Iva And V Of The Tau Subunit Of Escherichia Coli Dna Polymerase Iii And Interaction With The Alpha Subunit, Xun-Cheng Su, Slobodan Jergic, Max A Keniry, Nicholas E. Dixon, Gottfried Otting
Professor Nick E Dixon
The solution structure of the C-terminal Domain V of the τ subunit of E. coli DNA polymerase III was determined by nuclear magnetic resonance (NMR) spectroscopy. The fold is unique to τ subunits. Amino acid sequence conservation is pronounced for hydrophobic residues that form the structural core of the protein, indicating that the fold is representative for τ subunits from a wide range of different bacteria. The interaction between the polymerase subunits τ and α was studied by NMR experiments where α was incubated with full-length C-terminal domain (τC16), and domains shortened at the C-terminus by 11 and 18 residues, …
The Unstructured C-Terminus Of The Tau Subunit Of Escherichia Coli Dna Polymerase Iii Holoenzyme Is The Site Of Interaction With The Alpha Subunit, Slobodan Jergic, Kiyoshi Ozawa, Neal K. Williams, Xun-Cheng Su, Daniel D. Scott, Samir M. Hamdan, Jeffrey A. Crowther, Gottfried Otting, Nicholas E. Dixon
The Unstructured C-Terminus Of The Tau Subunit Of Escherichia Coli Dna Polymerase Iii Holoenzyme Is The Site Of Interaction With The Alpha Subunit, Slobodan Jergic, Kiyoshi Ozawa, Neal K. Williams, Xun-Cheng Su, Daniel D. Scott, Samir M. Hamdan, Jeffrey A. Crowther, Gottfried Otting, Nicholas E. Dixon
Professor Nick E Dixon
The τ subunit of Escherichia coli DNA polymerase III holoenzyme interacts with the α subunit through its C-terminal Domain V, τC16. We show that the extreme C-terminal region of τC16 constitutes the site of interaction with α. The τC16 domain, but not a derivative of it with a C-terminal deletion of seven residues (τC16Δ7), forms an isolable complex with α. Surface plasmon resonance measurements were used to determine the dissociation constant (KD) of the α−τC16 complex to be ∼260 pM. Competition with immobilized τC16 by τC16 derivatives for binding to α gave values of KD of 7 μM for the …
Reactions Of Simple And Peptidic Alpha-Carboxylate Radical Anions With Dioxygen In The Gas Phase, Tony Ly, Benjamin B. Kirk, Pramesh I. Hettiarachchi, Berwyck L. Poad, Adam J. Trevitt, Gabriel Da Silva, Stephen J. Blanksby
Reactions Of Simple And Peptidic Alpha-Carboxylate Radical Anions With Dioxygen In The Gas Phase, Tony Ly, Benjamin B. Kirk, Pramesh I. Hettiarachchi, Berwyck L. Poad, Adam J. Trevitt, Gabriel Da Silva, Stephen J. Blanksby
Berwyck L. J. Poad
α-Carboxylate radical anions are potential reactive intermediates in the free radical oxidation of biological molecules (e.g., fatty acids, peptides and proteins). We have synthesised well-defined α-carboxylate radical anions in the gas phase by UV laser photolysis of halogenated precursors in an ion-trap mass spectrometer. Reactions of isolated acetate (CH2CO 2-) and 1-carboxylatobutyl (CH3CH 2CH2CHCO2-) radical anions with dioxygen yield carbonate (CO3-) radical anions and this chemistry is shown to be a hallmark of oxidation in simple and alkyl-substituted cross-conjugated species. Previous solution phase studies have shown that Cα-radicals in peptides, formed from free radical damage, combine with dioxygen to form …
Reactions Of Simple And Peptidic Alpha-Carboxylate Radical Anions With Dioxygen In The Gas Phase, Tony Ly, Benjamin B. Kirk, Pramesh I. Hettiarachchi, Berwyck L. Poad, Adam J. Trevitt, Gabriel Da Silva, Stephen J. Blanksby
Reactions Of Simple And Peptidic Alpha-Carboxylate Radical Anions With Dioxygen In The Gas Phase, Tony Ly, Benjamin B. Kirk, Pramesh I. Hettiarachchi, Berwyck L. Poad, Adam J. Trevitt, Gabriel Da Silva, Stephen J. Blanksby
Stephen Blanksby
α-Carboxylate radical anions are potential reactive intermediates in the free radical oxidation of biological molecules (e.g., fatty acids, peptides and proteins). We have synthesised well-defined α-carboxylate radical anions in the gas phase by UV laser photolysis of halogenated precursors in an ion-trap mass spectrometer. Reactions of isolated acetate (CH2CO 2-) and 1-carboxylatobutyl (CH3CH 2CH2CHCO2-) radical anions with dioxygen yield carbonate (CO3-) radical anions and this chemistry is shown to be a hallmark of oxidation in simple and alkyl-substituted cross-conjugated species. Previous solution phase studies have shown that Cα-radicals in peptides, formed from free radical damage, combine with dioxygen to form …
Subunit Exchange Of Polydisperse Proteins: Mass Spectrometry Reveals Consequences Of Αa-Crystallin Truncation, J. Andrew Aquilina, Justin Benesch, Lin Lin Ding, Orna Yaron, Joseph Horwitz, Carol Robinson
Subunit Exchange Of Polydisperse Proteins: Mass Spectrometry Reveals Consequences Of Αa-Crystallin Truncation, J. Andrew Aquilina, Justin Benesch, Lin Lin Ding, Orna Yaron, Joseph Horwitz, Carol Robinson
J. A. Aquilina
The small heat shock protein, α-crystallin, plays a key role in maintaining lens transparency by chaperoning structurally compromised proteins. This is of particular importance in the human lens, where proteins are exposed to post-translational modifications over the life-time of an individual. Here, we examine the structural and functional consequences of one particular modification of αA-crystallin involving the truncation of 5 C-terminal residues (αA1–168). Using novel mass spectrometry approaches and established biophysical techniques, we show that αA1–168 forms oligomeric assemblies with a lower average molecular mass than wild-type αA-crystallin (αAWT). Also apparent from the mass spectra of both αAWT and αA1–168 …
3-Hydroxykynurenine Oxidizes Alpha-Crystallin: Potential Role In Cataractogenesis, Roger Truscott, Andrew Aquilina, Peter Hains, Anastasia Korlimbinis
3-Hydroxykynurenine Oxidizes Alpha-Crystallin: Potential Role In Cataractogenesis, Roger Truscott, Andrew Aquilina, Peter Hains, Anastasia Korlimbinis
J. A. Aquilina
No abstract provided.
Evidence For Specific Subunit Distribution And Interactions In The Quaternary Structure Of Α-Crystallin, Amie M. Morris, J Andrew Aquilina
Evidence For Specific Subunit Distribution And Interactions In The Quaternary Structure Of Α-Crystallin, Amie M. Morris, J Andrew Aquilina
J. A. Aquilina
The quaternary structure of alpha-crystallin is dynamic, a property which has thwarted crystallographic efforts towards structural characterization. In this study, we have used collision-induced dissociation mass spectrometry to examine the architecture of the polydisperse assemblies of alpha-crystallin. For total alpha-crystallin isolated directly from fetal calf lens using size-based chromatography, the alpha B-crystallin subunit was found to be preferentially dissociated from the oligomers, despite being significantly less abundant overall than the alpha A-crystallin subunits. Furthermore, upon mixing molar equivalents of purified alpha A- and alpha B-crystallin, the levels of their dissociation were found to decrease and increase, respectively, with time. Interestingly …
Reactions Of Simple And Peptidic Alpha-Carboxylate Radical Anions With Dioxygen In The Gas Phase, Tony Ly, Benjamin B. Kirk, Pramesh I. Hettiarachchi, Berwyck L. Poad, Adam J. Trevitt, Gabriel Da Silva, Stephen J. Blanksby
Reactions Of Simple And Peptidic Alpha-Carboxylate Radical Anions With Dioxygen In The Gas Phase, Tony Ly, Benjamin B. Kirk, Pramesh I. Hettiarachchi, Berwyck L. Poad, Adam J. Trevitt, Gabriel Da Silva, Stephen J. Blanksby
Adam Trevitt
α-Carboxylate radical anions are potential reactive intermediates in the free radical oxidation of biological molecules (e.g., fatty acids, peptides and proteins). We have synthesised well-defined α-carboxylate radical anions in the gas phase by UV laser photolysis of halogenated precursors in an ion-trap mass spectrometer. Reactions of isolated acetate (CH2CO 2-) and 1-carboxylatobutyl (CH3CH 2CH2CHCO2-) radical anions with dioxygen yield carbonate (CO3-) radical anions and this chemistry is shown to be a hallmark of oxidation in simple and alkyl-substituted cross-conjugated species. Previous solution phase studies have shown that Cα-radicals in peptides, formed from free radical damage, combine with dioxygen to form …
The Effect Of Small Molecules In Modulating The Chaperone Activity Of Alpha B-Crystallin Against Ordered And Disordered Protein Aggregation, Heath Ecroyd, John Carver
The Effect Of Small Molecules In Modulating The Chaperone Activity Of Alpha B-Crystallin Against Ordered And Disordered Protein Aggregation, Heath Ecroyd, John Carver
Heath Ecroyd
Protein aggregation can proceed via disordered or ordered mechanisms, with the latter being associated with amyloid fibril formation, which has been linked to a number of debilitating conditions including Alzheimer's, Parkinson's and Creutzfeldt-Jakob diseases. Small heat-shock proteins (sHsps), such as alpha B-crystallin, act as chaperones to prevent protein aggregation and are thought to play a key role in the prevention of protein-misfolding diseases. In this study, we have explored the potential for small molecules such as arginine and guanidine to affect the chaperone activity of alpha B-crystallin against disordered (amorphous) and ordered (amyloid fibril) forms of protein aggregation. The effect …
Amyloid Fibril Formation By Bovine Milk Alpha(S2)-Casein Occurs Under Physiological Conditions Yet Is Prevented By Its Natural Counterpart, Alpha(S1)-Casein, David Thorn, Heath Ecroyd, M Sunde, Stephen Poon, John Carver
Amyloid Fibril Formation By Bovine Milk Alpha(S2)-Casein Occurs Under Physiological Conditions Yet Is Prevented By Its Natural Counterpart, Alpha(S1)-Casein, David Thorn, Heath Ecroyd, M Sunde, Stephen Poon, John Carver
Heath Ecroyd
The calcified proteinaceous deposits, or corpora amylacea, of bovine mammary tissue often comprise a network of amyloid fibrils, the origins of which have not been fully elucidated. Here, we demonstrate by transmission electron microscopy, dye binding assays, and X-ray fiber diffraction that bovine milk alpha(s2)-casein, a protein synthesized and secreted by mammary epithelial cells, readily forms fibrils in vitro. As a component of whole alpha(s)-casein, alpha(s2)-casein was separated from alpha(s1)-casein under nonreducing conditions via cation-exchange chromatography. Upon incubation at neutral pH and 37 degrees C, the spherical particles typical of alpha(s2)-casein rapidly converted to twisted, ribbon-like fibrils similar to 12 …
The Interaction Of Alphab-Crystallin With Mature Alpha-Synuclein Amyloid Fibrils Inhibits Their Elongation, Christopher A. Waudby, Tuomas P. J Knowles, Glyn L. Devlin, Jeremy N. Skepper, Heath Ecroyd, John A. Carver, Mark E. Welland, John Christodoulou, Christopher M. Dobson, Sarah Meehan
The Interaction Of Alphab-Crystallin With Mature Alpha-Synuclein Amyloid Fibrils Inhibits Their Elongation, Christopher A. Waudby, Tuomas P. J Knowles, Glyn L. Devlin, Jeremy N. Skepper, Heath Ecroyd, John A. Carver, Mark E. Welland, John Christodoulou, Christopher M. Dobson, Sarah Meehan
Heath Ecroyd
alphaB-Crystallin is a small heat-shock protein (sHsp) that is colocalized with alpha-synuclein (alphaSyn) in Lewy bodies—the pathological hallmarks of Parkinson's disease—and is an inhibitor of alphaSyn amyloid fibril formation in an ATP-independent manner in vitro. We have investigated the mechanism underlying the inhibitory action of sHsps, and here we establish, by means of a variety of biophysical techniques including immunogold labeling and nuclear magnetic resonance spectroscopy, that alphaB-crystallin interacts with alphaSyn, binding along the length of mature amyloid fibrils. By measurement of seeded fibril elongation kinetics, both in solution and on a surface using a quartz crystal microbalance, this binding …
Amyloid Fibril Formation By Bovine Milk Kappa-Casein And Its Inhibition By The Molecular Chaperones Alpha-S And Beta-Casein, Mark Wilson, David Thorn, Agata Rekas, S. L Gras, Christopher Dobson, Sarah Meehan, Cait Macphee, M Sunde
Amyloid Fibril Formation By Bovine Milk Kappa-Casein And Its Inhibition By The Molecular Chaperones Alpha-S And Beta-Casein, Mark Wilson, David Thorn, Agata Rekas, S. L Gras, Christopher Dobson, Sarah Meehan, Cait Macphee, M Sunde
Mark R Wilson
No abstract provided.
Heat Shock Protein 70 Inhibits Alpha-Synuclein Fibril Formation Via Preferential Binding To Prefibrillar Species, Mark Wilson, M. M. Dedmon, J. Christodoulou, Christopher Dobson
Heat Shock Protein 70 Inhibits Alpha-Synuclein Fibril Formation Via Preferential Binding To Prefibrillar Species, Mark Wilson, M. M. Dedmon, J. Christodoulou, Christopher Dobson
Mark R Wilson
No abstract provided.