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Full-Text Articles in Social and Behavioral Sciences

Kinase Inhibitory, Haemolytic And Cytotoxic Activity Of Three Deep-Water Sponges From North Western Australia And Their Fatty Acid Composition, Ana Zivanovic, Natalie J. Pastro, Jane Fromont, Murray Thomson, Danielle Skropeta Nov 2013

Kinase Inhibitory, Haemolytic And Cytotoxic Activity Of Three Deep-Water Sponges From North Western Australia And Their Fatty Acid Composition, Ana Zivanovic, Natalie J. Pastro, Jane Fromont, Murray Thomson, Danielle Skropeta

Danielle Skropeta

The c-AMP dependent protein kinase (PKA) inhibition, haemolytic activity, and cytoxicity of 21 extracts obtained from North Western Australian sponges collected from depths of 84-135 m were investigated. Hexane extracts from Ircinia/Sarcotragus sp. and Geodia sp. displayed PKA inhibitory activities of 100 and 97% respectively (at 100 μg/mL), while aq. methanol extracts from Haliclona sp. exhibited potent haemolytic activity (75%) and hexane extracts from Geodia sp. were highly toxic (88%) to the brine shrimp Artemia franciscana. As the non-polar extracts gave the greatest PKA inhibition, these were further analysed by GC-MS and 29 fatty acids were identified in the highest …


Deep-Sea Natural Products, Danielle Skropeta Nov 2013

Deep-Sea Natural Products, Danielle Skropeta

Danielle Skropeta

This review covers the 390 novel marine natural products described to date from deep-water (>50 m)marine fauna, with details on the source organism, its depth and country of origin, along with anyreported biological activity of the metabolites. Relevant synthetic studies on the deep-sea naturalproducts have also been included.


Misidentification Of Tansy, Tanacetum Macrophyllum, As Yarrow, Achillea Grandifolia: A Health Risk Or Benefit?, Niko Radulovic, Polina Blagojevic, Danielle Skropeta, Aleksandra Zarubica, Bojan Zlatkovic, Radosav Palic´ Nov 2013

Misidentification Of Tansy, Tanacetum Macrophyllum, As Yarrow, Achillea Grandifolia: A Health Risk Or Benefit?, Niko Radulovic, Polina Blagojevic, Danielle Skropeta, Aleksandra Zarubica, Bojan Zlatkovic, Radosav Palic´

Danielle Skropeta

Tansy, Tanacetum macrophyllum (Waldst. & Kit.) Sch. Bip., is often misidentified by herb collectors as yarrow, Achillea grand folia Friv. With the former, cases of poisoning induced by its ingestion are well documented, but the latter is widely used for ethnopharmacological purposes. The aim of this study was to estimate, based on the volatile metabolite profiles of the two species, the potential health risk connected with their misidentification. GC and GC-MS analysis of the essential oils hydrodistilled using a Clevenger-type apparatus from A. grandifolia, T macrophyllum, and two plant samples (reputedly of A. grandifolia, but in fact mixtures of A. …


Kinase Inhibitors From Marine Sponges, Danielle Skropeta, Natalie Pastro, Ana Zivanovic Nov 2013

Kinase Inhibitors From Marine Sponges, Danielle Skropeta, Natalie Pastro, Ana Zivanovic

Danielle Skropeta

Protein kinases play a critical role in cell regulation and their deregulation is a contributing factor in an increasing list of diseases including cancer. Marine sponges have yielded over 70 novel compounds to date that exhibit significant inhibitory activity towards a range of protein kinases. These compounds, which belong to diverse structural classes, are reviewed herein, and ordered based upon the kinase that they inhibit. Relevant synthetic studies on the marine natural product kinase inhibitors have also been included.


Structures, Biological Activities And Phylogenetic Relationships Of Terpenoids From Marine Ciliates Of The Genus Euplotes, Graziano Guella, Danielle Skropeta, Graziano Di Giuseppe, Fernando Dini Nov 2013

Structures, Biological Activities And Phylogenetic Relationships Of Terpenoids From Marine Ciliates Of The Genus Euplotes, Graziano Guella, Danielle Skropeta, Graziano Di Giuseppe, Fernando Dini

Danielle Skropeta

In the last two decades, large scale axenic cell cultures of the marine species comprising the family Euplotidae have resulted in the isolation of several new classes of terpenoids with unprecedented carbon skeletons including the (i) euplotins, highly strained acetylated sesquiterpene hemiacetals; (ii) raikovenals, built on the bicyclo[3.2.0]heptane ring system; (iii) rarisetenolides and focardins containing an octahydroazulene moiety; and (iv) vannusals, with a unique C-30 backbone. Their complex structures have been elucidated through a combination of nuclear magnetic resonance spectroscopy, mass spectrometry, molecular mechanics and quantum chemical calculations. Despite the limited number of biosynthetic experiments having been performed, the large …


Average Mass Scan Of The Total Ion Chromatogram Versus Percentage Chemical Composition In Multivariate Statistical Comparison Of Complex Volatile Mixtures, Niko Radulovic, Polina Blagojevic, Danielle Skropeta Nov 2013

Average Mass Scan Of The Total Ion Chromatogram Versus Percentage Chemical Composition In Multivariate Statistical Comparison Of Complex Volatile Mixtures, Niko Radulovic, Polina Blagojevic, Danielle Skropeta

Danielle Skropeta

The analysis of complex volatile mixtures by gas chromatography-mass spectrometry (GC-MS) is a time-consuming process. It involves separation and identification of the components based on their retention times and fragmentation patterns, followed by determination of their relative percentages from integration of their peak areas. Herein we show that multivariate statistical analysis of the relative abundances of the m/z values obtained from the average mass scans (AMS) of the complex mixture is a faster and potentially more reliable method of assessing these mixtures. To achieve this, 15 model complex mixtures, were prepared comprising varying amounts of 10 different constituents. The AMS …


Synthesis And Anti-Leukaemic Activity Of Pyrrolo[3,2,1-Hi]Indole-1,2- Diones, Pyrrolo[3,2,1-Ij]Quinoline-1,2-Diones And Other Polycyclic Isatin Derivatives, Lidia Matesic, Julie M. Locke, Kara Vine, Marie Ranson, John B. Bremner, Danielle Skropeta Nov 2013

Synthesis And Anti-Leukaemic Activity Of Pyrrolo[3,2,1-Hi]Indole-1,2- Diones, Pyrrolo[3,2,1-Ij]Quinoline-1,2-Diones And Other Polycyclic Isatin Derivatives, Lidia Matesic, Julie M. Locke, Kara Vine, Marie Ranson, John B. Bremner, Danielle Skropeta

Danielle Skropeta

To further expand the structure–cytotoxic activity relationships of isatin derivatives and to reduce flexibility in substituent groups at nitrogen, 20 analogues incorporating a ring system between the N1 and C7 atoms of isatin were prepared using a variety of synthetic strategies. This yielded pyrroloindole-, pyrroloquinoline-, pyrroloacridine-, pyrrolophenanthridine- and benzopyrrolophenanthridine-based systems with embedded isatin moieties, the latter possessing a novel carbon skeleton. These compounds were subsequently assessed for their in vitro cytotoxicity against human U937 lymphoma cells, with the brominated pyrroloacridine dione 27 showing the most promising activity (IC50 3.01 μM) after 24 h.


C-Amp Dependent Protein Kinase A Inhibitory Activity Of Six Algal Extracts From South Eastern Australia And Their Fatty Acid Composition, Ana Zivanovic, Danielle Skropeta Nov 2013

C-Amp Dependent Protein Kinase A Inhibitory Activity Of Six Algal Extracts From South Eastern Australia And Their Fatty Acid Composition, Ana Zivanovic, Danielle Skropeta

Danielle Skropeta

c-AMP dependent protein kinase (protein kinase A, PKA) is an important enzyme involved in the regulation of an increasing number of physiological processes including immune function, cardiovascular disease, memory disorders and cancer. The objective of this study was to evaluate the PKA inhibitory activity of a range of algal extracts, along with their fatty acid composition. Six algal species were investigated including two Chlorophyta (Codium dimorphum and Ulva lactuca), two Phaeophyta (Phyllospora comosa and Sargassum sp.) and two Rhodophyta (Prionitis linearis and Corallina vancouveriensis), with the order of PKA inhibitory activity of their extracts identified as follows: brown seaweeds > red …


Learning How To Be An Academic - The Story Of A New Academic In The Sciences, Danielle Skropeta Nov 2013

Learning How To Be An Academic - The Story Of A New Academic In The Sciences, Danielle Skropeta

Danielle Skropeta

No abstract provided.


Solid-State And Solution-Phase Conformations Of Pseudoproline-Containing Dipeptides, James R. Cochrane, Nima Sayyadi, Danielle Skropeta, Peter Turner, Jack K. Clegg, Katrina A. Jolliffe Nov 2013

Solid-State And Solution-Phase Conformations Of Pseudoproline-Containing Dipeptides, James R. Cochrane, Nima Sayyadi, Danielle Skropeta, Peter Turner, Jack K. Clegg, Katrina A. Jolliffe

Danielle Skropeta

The conformations of 14 threonine-derived pseudoproline-containing dipeptides (including four d-allo-Thr derivatives) have been investigated by NMR. In solution, the major conformer observed for all dipeptides is that in which the amide bond between the pseudoproline and the preceding amino acid is cis. For dipeptides in which the N-terminus is protected, the ratio of cis- to trans-conformers does not depend significantly on the side chain of the N-terminal amino acid, or the stereochemistry of the Thr residue. However, for dipeptides bearing a free N-terminus, there are significant differences in the ratios of cis- to trans-conformers depending on the side chain present. …


Removal Of Trace Organic Contaminants By Nitrifying Activated Sludge And Whole-Cell And Crude Enzyme Extract Of Trametes Versicolor, Shufan Yang, Faisal I. Hai, Long D. Nghiem, Felicity Roddick, William E. Price Oct 2013

Removal Of Trace Organic Contaminants By Nitrifying Activated Sludge And Whole-Cell And Crude Enzyme Extract Of Trametes Versicolor, Shufan Yang, Faisal I. Hai, Long D. Nghiem, Felicity Roddick, William E. Price

William E. Price

The resistance of certain anthropogenic trace organic contaminants (TrOCs) to conventional wastewater treatment and their potential adverse effects on human and ecological health raise significant concerns and have prompted research on their bioremediation by white-rot fungi. This study compared the removal efficiencies of four widespread TrOCs: carbamazepine (CBZ), sulfamethoxazole (SMX), bisphenol A (BPA) and diclofenac (DCF), by nitrifying activated sludge as well as whole-cell and extracellular enzyme (laccase) extract of the white-rot fungus Trametes versicolor. Fungal whole-cell culture removed only BPA and DCF but with high efficiencies (>90%) while the mixed nitrifying culture removed all compounds, although by levels …


Synthesis Of Reaction-Ready 6,6 '-Biindole And 6,6 '-Biisatin Via Palladium(Ii)-Catalysed Intramolecular C-H Functionalisation, Allan B. Gamble, Paul A. Keller Sep 2013

Synthesis Of Reaction-Ready 6,6 '-Biindole And 6,6 '-Biisatin Via Palladium(Ii)-Catalysed Intramolecular C-H Functionalisation, Allan B. Gamble, Paul A. Keller

Paul Keller

The first synthesis of a 6,6'-biindole and 6,6'-biisatin scaffold is reported with the penultimate step being the formation of the di-heterocyclic ring by Pd(II)-catalysed intramolecular C-H functionalisation and Sandmeyer cyclisation, respectively.


The First Syntheses Of Enantiopure 2,2 '-Biindoline, Steven M. Wales, Anthony C. Willis, Paul A. Keller Sep 2013

The First Syntheses Of Enantiopure 2,2 '-Biindoline, Steven M. Wales, Anthony C. Willis, Paul A. Keller

Paul Keller

The first two syntheses of chiral 2,2'-biindoline are reported either in five steps from 2,2'-bioxirane, or three steps from 2,2'-biaziridine, both with exceptional enantiopurity


Reductive Ring Opening Reactions Of Diphenyldihydrofullerenylpyrroles, William Hawkins, Paul A. Keller, Stephen G. Pyne Sep 2013

Reductive Ring Opening Reactions Of Diphenyldihydrofullerenylpyrroles, William Hawkins, Paul A. Keller, Stephen G. Pyne

Paul Keller

The reductive ring opening reaction conditions for the simple [60]fullerenyldihydropyrrole 1 have been optimized to include acetic acid in the reaction mixture to rapidly protonate the anionic intermediate. Under these conditions, the ring opened dihydrofullerene 2 was obtained in 68% yield. Under slightly modified conditions and at −78 °C, the reductive bis-ring opening of the tethered trans-4 isomer 3 provided the novel racemic bis-dihydrofullerenyl derivative 7.


Revealing Indigenous Indonesian Traditional Medicine: Anti-Infective Agents, Paul A. Keller, Ari Satia Nugraha Sep 2013

Revealing Indigenous Indonesian Traditional Medicine: Anti-Infective Agents, Paul A. Keller, Ari Satia Nugraha

Paul Keller

Indonesia is rich in medicinal plants which the population has used traditionally from generation to generation for curing diseases. Our interest in the treatment of infectious diseases has lead to the investigation of traditional Indonesian treatments. In this review, we present a comprehensive review of ethnopharmacologically directed screening in Indonesian medicinal plants to search for new anti-viral, antimalarial, anti-bacterial and anti-fungal agents. Some potent drug leads have been isolated from Indonesian medicinal plants. Further research is still required for the lead development as well as the search for new bioactive compounds from the enormous medicinal plant resources.


Binaphthyl-Anchored Antibacterial Tripeptide Derivatives With Hydrophobic C-Terminal Amino Acid Variations, John Bremner, Paul A. Keller, Stephen Pyne, Mark Robertson, Kandasamy Sakthivel, Kittiya Somphol, Dean Baylis, Jonathon A Coates, John Deadman, Dharshini Jeevarajah, David I. Rhodes Sep 2013

Binaphthyl-Anchored Antibacterial Tripeptide Derivatives With Hydrophobic C-Terminal Amino Acid Variations, John Bremner, Paul A. Keller, Stephen Pyne, Mark Robertson, Kandasamy Sakthivel, Kittiya Somphol, Dean Baylis, Jonathon A Coates, John Deadman, Dharshini Jeevarajah, David I. Rhodes

Paul Keller

The facile synthesis of seven new dicationic tripeptide benzyl ester derivatives, with hydrophobic group variations in the C-terminal amino acid component, is described. Moderate to good activity was seen against Gram-positive bacteria in vitro. One cyclohexyl-substituted compound 2c was tested more widely and showed good potency (MIC values ranging from 2–4 μg/mL) against antibiotic-resistant strains of Staphylococcus aureus and Enterococci (VRE, VSE), and against Staphylococcus epidermidis.


Synthesis Of Novel N-Protected Hydrophobic Phenylalanines And Their Application In Potential Antibacterials, Timothy P. Boyle, J. B. Bremner, Jonathan A. Coates, John Deadman, Paul A. Keller, Stephen G. Pyne, Kittiya Somphol Sep 2013

Synthesis Of Novel N-Protected Hydrophobic Phenylalanines And Their Application In Potential Antibacterials, Timothy P. Boyle, J. B. Bremner, Jonathan A. Coates, John Deadman, Paul A. Keller, Stephen G. Pyne, Kittiya Somphol

Paul Keller

An efficient synthesis of two new N-acetyl-4’-arylphenylalanines is described together with their incorporation in to a number of cationic peptoid antibacterial agents, one of which had an MIC of 7.8 μg/mL against Staphylococcus aureus.


Phytochemical And Biological Activity Studies Of The Bhutanese Medicinal Plant Corydalis Crispa, Phurpa Wangchuk, Paul A. Keller, Stephen G. Pyne, Thanapat Sastraruji, Malai Taweechotipatr, Roonglawan Rattanajak, Aunchalee Tonsomboon, Sumalee Kamchonwongpaisan Sep 2013

Phytochemical And Biological Activity Studies Of The Bhutanese Medicinal Plant Corydalis Crispa, Phurpa Wangchuk, Paul A. Keller, Stephen G. Pyne, Thanapat Sastraruji, Malai Taweechotipatr, Roonglawan Rattanajak, Aunchalee Tonsomboon, Sumalee Kamchonwongpaisan

Paul Keller

The chemical constituents and biological activities of Corydalis crispa (Fumariaceae) were investigated for the first time. The phytochemical study resulted in the isolation of nine known isoquinoline alkaloids: protopine (1), 13-oxoprotopine (2), 13-oxocryptopine (3), stylopine (4), coreximine (5), rheagenine (6), ochrobirine (7), sibiricine (8) and bicuculline (9), with complete NMR data for 2 and 3 provided here for the first time. Crude extracts exhibitedsignificant anti-inflammatory (p < 0.01) activity against TNF-alpha production in LPS activated THP-1 cells. The acetylcholinesterase inhibitory activity of compounds 2, 4 and 7 and the antiplasmodial activity of compound 5 against P. falciparum strains TM4/8.2 and K1CB1 …


An Assessment Of The Bhutanese Traditional Medicine For Its Ethnopharmacology, Ethnobotany And Ethnoquality: Textual Understanding And The Current Practices, Phurpa Wangchuk, Stephen G. Pyne, Paul A. Keller Sep 2013

An Assessment Of The Bhutanese Traditional Medicine For Its Ethnopharmacology, Ethnobotany And Ethnoquality: Textual Understanding And The Current Practices, Phurpa Wangchuk, Stephen G. Pyne, Paul A. Keller

Paul Keller

Ethnopharmacological relevance : This study involves the assessment of the Bhutanese traditional medicine (BTM) which was integrated with the mainstream biomedicine in 1967 to provide primary health care services in the country. It caters to 20-30% of the daily out-patients within 49 traditional medicine units attached to 20 district modern hospitals and 29 Basic Health Units in the country. Aim of the study : This study presents the ethnopharmacological, ethnobotanical and the ethnoquality concepts in relation to mainstream Tibetan medicine and describes the current practices of BTM. Materials and methods : Experienced BTM practitioners (Drung-tshos and Smen-pas) were selected using …


Antimalarial Alkaloids From A Bhutanese Traditional Medicinal Plant Corydalis Dubia, Phurpa Wangchuk, Paul A. Keller, Stephen G. Pyne, Anthony C. Willis, Sumalee Kamchonwongpaisan Sep 2013

Antimalarial Alkaloids From A Bhutanese Traditional Medicinal Plant Corydalis Dubia, Phurpa Wangchuk, Paul A. Keller, Stephen G. Pyne, Anthony C. Willis, Sumalee Kamchonwongpaisan

Paul Keller

Ethnopharmacological relevance: Corydalis dubia is used in Bhutanese traditional medicine as a febrifuge and for treating infections in the blood, liver and bile which correlate to the signs and symptoms of malarial and microbial infections. Aim of the study: To validate the ethnopharmacological uses of the plant and to discover potential new therapeutic drug leads. Materials and methods C. dubia was collected from Bhutan and the alkaloids were obtained using acid–base fractionation and separation by repeated column and preparative plate chromatography. The alkaloids were identified from analysis of their physiochemical and spectroscopic data and were tested for antiplasmodial, antimicrobial and …


Structural Re-Assignment Of The Mono- And Bis-Addition Products From The Addition Reactions Of N-(Diphenylmethylene)Glycinate Esters To [60]Fullerene Under Bingel Conditions, Graham E Ball, Glenn Ashley Burley, Leila Chaker, William Hawkins, James Williams, Paul A. Keller, Stephen G. Pyne Sep 2013

Structural Re-Assignment Of The Mono- And Bis-Addition Products From The Addition Reactions Of N-(Diphenylmethylene)Glycinate Esters To [60]Fullerene Under Bingel Conditions, Graham E Ball, Glenn Ashley Burley, Leila Chaker, William Hawkins, James Williams, Paul A. Keller, Stephen G. Pyne

Paul Keller

The addition of N-(diphenylmethylene)glycinate esters (Ph2C=NCH2CO2R) to [60]fullerene under Bingel conditions gives [60]fullerenyldihydropyrroles and not methano[60]fullerenyl iminoesters [C60C(CO2R)(N=CPh2)] as previously reported. Unequivocal evidence for the structure of C60C(CO2Et)(N=CPh2) was provided by INADEQUATE NMR studies on 13C enriched material. New mechanistic details are proposed to account for the formation of [60]fullerenyldihydropyrroles and their reductive ring-opening reactions.


Bacterial Filtration Using Carbon Nanotube/Antibiotic Buckypaper Membranes, Luke J. Sweetman, Leighton J. Alcock, Jason D. Mcarthur, Elise M. Stewart, Gerry Triani, Marc In Het Panhuis, Stephen F. Ralph Jul 2013

Bacterial Filtration Using Carbon Nanotube/Antibiotic Buckypaper Membranes, Luke J. Sweetman, Leighton J. Alcock, Jason D. Mcarthur, Elise M. Stewart, Gerry Triani, Marc In Het Panhuis, Stephen F. Ralph

Luke Sweetman

The preparation of free-standing carbon nanotube “buckypaper” (BP) membranes consisting of either single-walled carbon nanotubes (SWNTs) or multi-walled carbon nanotubes (MWNTs), and the antibiotic ciprofloxacin (cipro), is reported. The electrical, mechanical and morphological properties of these membranes have been characterised and are compared to those of the corresponding buckypaper membranes containing the surfactant Triton X-100 (Trix). Analysis of scanning electron microscopic images of the surfaces of SWNT/cipro and SWNT/Trix (Trix  =  Triton X-100) buckypapers revealed that the diameter of their surface pores was significantly smaller than that of the corresponding materials prepared using MWNTs. Similarly, the average internal pore diameter …


Rapid Differentiation Of Isomeric Lipids By Photodissociation Mass Spectrometry Of Fatty Acid Derivatives, Huong T. Pham, Adam J. Trevitt, Todd W. Mitchell, Stephen J. Blanksby Jul 2013

Rapid Differentiation Of Isomeric Lipids By Photodissociation Mass Spectrometry Of Fatty Acid Derivatives, Huong T. Pham, Adam J. Trevitt, Todd W. Mitchell, Stephen J. Blanksby

Adam Trevitt

RATIONALE Both traditional electron ionization and electrospray ionization tandem mass spectrometry have demonstrated limitations in the unambiguous identification of fatty acids. In the former case, high electron energies lead to extensive dissociation of the radical cations from which little specific structural information can be obtained. In the latter, conventional collision-induced dissociation (CID) of even-electron ions provides little intra-chain fragmentation and thus few structural diagnostics. New approaches that harness the desirable features of both methods, namely radical-driven dissociation with discrete energy deposition, are thus required. METHODS Herein we describe the derivatization of a structurally diverse suite of fatty acids as 4-iodobenzyl …


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 Jul 2013

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, …


Effect Of Protein Stabilization On Charge State Distribution In Positive- And Negative Ion Electrospray Ionization Mass Spectra, Stephen J. Watt, Margaret Sheil, Jennifer L. Beck, Pavel Prosselkov, Gottfried Otting, Nicholas E. Dixon Jul 2013

Effect Of Protein Stabilization On Charge State Distribution In Positive- And Negative Ion Electrospray Ionization Mass Spectra, Stephen J. Watt, Margaret Sheil, Jennifer L. Beck, Pavel Prosselkov, Gottfried Otting, Nicholas E. Dixon

Professor Nick E Dixon

Changes in protein conformation are thought to alter charge state distributions observed in electrospray ionization mass spectra (ESI-MS) of proteins. In most cases, this has been demonstrated by unfolding proteins through acidification of the solution. This methodology changes the properties of the solvent so that changes in the ESI-MS charge envelopes from conformational changes are difficult to separate from the effects of changing solvent on the ionization process. A novel strategy is presented enabling comparison of ESI mass spectra of a folded and partially unfolded protein of the same amino acid sequence subjected to the same experimental protocols and conditions. …


Escherichia Coli Single-Stranded Dna-Binding Protein: Nanoesi-Ms Studies Of Salt-Modulated Subunit Exchange And Dna Binding Transactions, Claire E. Mason, Slobodan Jergic, Allen Lo, Yao Wang, Nicholas E. Dixon, Jennifer L. Beck Jul 2013

Escherichia Coli Single-Stranded Dna-Binding Protein: Nanoesi-Ms Studies Of Salt-Modulated Subunit Exchange And Dna Binding Transactions, Claire E. Mason, Slobodan Jergic, Allen Lo, Yao Wang, Nicholas E. Dixon, Jennifer L. Beck

Professor Nick E Dixon

Single-stranded DNA-binding proteins (SSBs) are ubiquitous oligomeric proteins that bind with very high affinity to single-stranded DNA and have a variety of essential roles in DNA metabolism. Nanoelectrospray ionization mass spectrometry (nanoESI-MS) was used to monitor subunit exchange in full-length and truncated forms of the homotetrameric SSB from Escherichia coli. Subunit exchange in the native protein was found to occur slowly over a period of hours, but was significantly more rapid in a truncated variant of SSB from which the eight C-terminal residues were deleted. This effect is proposed to result from C-terminus mediated stabilization of the SSB tetramer, in …


Architecture And Conservation Of The Bacterial Dna Replication Machinery, An Underexploited Drug Target, Andrew Robinson, Rebecca J. Causer, Nicholas E. Dixon Jul 2013

Architecture And Conservation Of The Bacterial Dna Replication Machinery, An Underexploited Drug Target, Andrew Robinson, Rebecca J. Causer, Nicholas E. Dixon

Professor Nick E Dixon

"New antibiotics with novel modes of action are required to combat the growing threat posed by multi-drug resistant bacteria. Over the last decade, genome sequencing and other high-throughput techniques have provided tremendous insight into the molecular processes underlying cellular functions in a wide range of bacterial species. We can now use these data to assess the degree of conservation of certain aspects of bacterial physiology, to help choose the best cellular targets for development of new broad-spectrum antibacterials. DNA replication is a conserved and essential process, and the large number of proteins that interact to replicate DNA in bacteria are …


Characterization Of Cleavage Events In The Multifunctional Cilium Adhesin Mhp684 (P146) Reveals A Mechanism By Which Mycoplasma Hyopneumoniae Regulates Surface Topography, Daniel Bogema, Ania T. Deutscher, Lauren K. Woolley, Lisa M. Seymour, Benjamin B. A Raymond, Jessica L. Tacchi, Matthew P. Padula, Nicholas E. Dixon, F Chris Minion, Cheryl Jenkins, Mark J. Walker, Steven P. Djordjevic Jul 2013

Characterization Of Cleavage Events In The Multifunctional Cilium Adhesin Mhp684 (P146) Reveals A Mechanism By Which Mycoplasma Hyopneumoniae Regulates Surface Topography, Daniel Bogema, Ania T. Deutscher, Lauren K. Woolley, Lisa M. Seymour, Benjamin B. A Raymond, Jessica L. Tacchi, Matthew P. Padula, Nicholas E. Dixon, F Chris Minion, Cheryl Jenkins, Mark J. Walker, Steven P. Djordjevic

Professor Nick E Dixon

Mycoplasma hyopneumoniae causes enormous economic losses to swine production worldwide by colonizing the ciliated epithelium in the porcine respiratory tract, resulting in widespread damage to the mucociliary escalator, prolonged inflammation, reduced weight gain, and secondary infections. Protein Mhp684 (P146) comprises 1,317 amino acids, and while the N-terminal 400 residues display significant sequence identity to the archetype cilium adhesin P97, the remainder of the molecule is novel and displays unusual motifs. Proteome analysis shows that P146 preprotein is endogenously cleaved into three major fragments identified here as P50P146, P40P146, and P85P146 that reside on the cell surface. Liquid chromatography with tandem …


Defining The Structural Basis Of Human Plasminogen Binding By Streptococcal Surface Enolase, Amanda J. Cork, Slobodan Jergic, Sven Hammerschmidt, Bostjan Kobe, Vijay Pancholi, Justin L.P. Benesch, Carol V, Robinson, Nicholas E. Dixon, J Andrew Aquilina, Mark J. Walker Jul 2013

Defining The Structural Basis Of Human Plasminogen Binding By Streptococcal Surface Enolase, Amanda J. Cork, Slobodan Jergic, Sven Hammerschmidt, Bostjan Kobe, Vijay Pancholi, Justin L.P. Benesch, Carol V, Robinson, Nicholas E. Dixon, J Andrew Aquilina, Mark J. Walker

Professor Nick E Dixon

The flesh-eating bacterium group A Streptococcus (GAS) binds and activates human plasminogen, promoting invasive disease. Streptococcal surface enolase (SEN), a glycolytic pathway enzyme, is an identified plasminogen receptor of GAS. Here we used mass spectrometry (MS) to confirm that GAS SEN is octameric, thereby validating in silico modeling based on the crystal structure of S. pneumoniae -enolase. Site-directed mutagenesis of surface-located lysine residues (SENK252+255A, SENK304A, SENK334A, SENK344E, SENK435L and SEN434-435) was used to examine their roles in maintaining structural integrity, enzymatic function and plasminogen binding. Structural integrity of the GAS SEN octamer was retained for all mutants except SENK344E, as …


Essential Biological Processes Of An Emerging Pathogen: Dna Replication, Transcription, And Cell Division In Acinetobacter Spp., Andrew Robinson, Anthony J. Brzoska, Kylie M. Turner, Ryan Withers, Elizabeth J. Harry, Peter J. Lewis, Nicholas E. Dixon Jul 2013

Essential Biological Processes Of An Emerging Pathogen: Dna Replication, Transcription, And Cell Division In Acinetobacter Spp., Andrew Robinson, Anthony J. Brzoska, Kylie M. Turner, Ryan Withers, Elizabeth J. Harry, Peter J. Lewis, Nicholas E. Dixon

Professor Nick E Dixon

Species of the bacterial genus Acinetobacter are becoming increasingly important as a source of hospital-acquired infections (31, 185, 204). Acinetobacter spp. are ubiquitous nonmotile gammaproteobacteria, typified by metabolic versatility and a capacity for natural transformation (172, 204). The species of most clinical relevance is A. baumannii; however, pathogenic strains of A. lwoffi and A. baylyi have also been described (38, 185, 215).