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https://www.readbyqxmd.com/read/29353085/reactions-of-a-tetranuclear-pt-thiosemicarbazone-complex-with-model-proteins
#1
Tiziano Marzo, Francisco Navas, Damiano Cirri, Antonello Merlino, Giarita Ferraro, Luigi Messori, Adoracion G Quiroga
The tetranuclear Pt complex (PtL)4 (where L2- is the anion derived from para-isopropyl thiosemicarbazone) was first described in A.G. Quiroga et al., J. Med. Chem. 41, 1998, 1399-1408. (PtL)4 manifests antiproliferative properties toward various cancer cell lines being a promising anticancer drug candidate. Yet, details of its reactivity with biomolecules have not been elucidated. To this end, we investigated the reactions of (PtL)4 with a few model proteins, i.e. bovine pancreatic ribonuclease (RNase A), cytochrome c (Cyt c) and hen egg white lysozyme (Lysozyme), through electrospray ionization mass spectrometry and other biophysical methods...
January 10, 2018: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/29352597/potential-drug-targets-in-the-mycobacterium-tuberculosis-cytochrome-p450-system
#2
REVIEW
Paul R Ortiz de Montellano
The Mycobacterium tuberculosis genome encodes twenty cytochrome P450 enzymes, most or all of which appear to have specific physiological functions rather than being devoted to the removal of xenobiotics. However, in many cases their specific functions remain obscure. Considerable spectroscopic, biophysical, crystallographic, and catalytic information is available on nine of these cytochrome P450 enzymes, although gaps exist in our knowledge of even these enzymes. The available evidence indicates that at least three of the better-characterized enzymes are promising targets for antituberculosis drug discovery...
January 12, 2018: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/29352320/high-level-production-and-purification-in-a-functional-state-of-an-extrasynaptic-gamma-aminobutyric-acid-type-a-receptor-containing-%C3%AE-4%C3%AE-3%C3%AE-subunits
#3
Xiaojuan Zhou, Rooma Desai, Yinghui Zhang, Wojciech J Stec, Keith W Miller, Youssef Jounaidi
The inhibitory γ-aminobutyric acid type A receptors are implicated in numerous physiological processes, including cognition and inhibition of neurotransmission, rendering them important molecular targets for many classes of drugs. Functionally, the entire GABAAR family of receptors can be subdivided into phasic, fast acting synaptic receptors, composed of α-, β- and γ-subunits, and tonic extrasynaptic receptors, many of which contain the δ-subunit in addition to α- and β-subunits. Whereas the subunit arrangement of the former group is agreed upon, that of the αβδ GABAARs remains unresolved by electrophysiological and pharmacological research...
2018: PloS One
https://www.readbyqxmd.com/read/29352312/a-role-for-domain-i-of-the-hepatitis-c-virus-ns5a-protein-in-virus-assembly
#4
Chunhong Yin, Niluka Goonawardane, Hazel Stewart, Mark Harris
The NS5A protein of hepatitis C virus (HCV) plays roles in both virus genome replication and assembly. NS5A comprises three domains, of these domain I is believed to be involved exclusively in genome replication. In contrast, domains II and III are required for the production of infectious virus particles and are largely dispensable for genome replication. Domain I is highly conserved between HCV and related hepaciviruses, and is highly structured, exhibiting different dimeric conformations. To investigate the functions of domain I in more detail, we conducted a mutagenic study of 12 absolutely conserved and surface-exposed residues within the context of a JFH-1-derived sub-genomic replicon and infectious virus...
January 19, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29352252/towards-an-experimental-classification-system-for-membrane-active-peptides
#5
G D Brand, M H S Ramada, T C Genaro-Mattos, C Bloch
Mature proteins can act as potential sources of encrypted bioactive peptides that, once released from their parent proteins, might interact with diverse biomolecular targets. In recent work we introduced a systematic methodology to uncover encrypted intragenic antimicrobial peptides (IAPs) within large protein sequence libraries. Given that such peptides may interact with membranes in different ways, resulting in distinct observable outcomes, it is desirable to develop a predictive methodology to categorize membrane active peptides and establish a link to their physicochemical properties...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29351890/evolutionary-mechanisms-studied-through-protein-fitness-landscapes
#6
REVIEW
Aneth S Canale, Pamela A Cote-Hammarlof, Julia M Flynn, Daniel Na Bolon
Biology has, and continues to be, shaped by evolutionary mechanisms. Within the past decade, local fitness landscapes have become experimentally tractable and are providing new perspectives on evolutionary mechanisms. Powered by next-generation sequencing, the impacts of all individual amino acid substitutions on function have been quantified for dozens of proteins. These fitness maps have been utilized to investigate the biophysical underpinnings of existing protein function as well as the appearance and enhancement of new protein functions...
January 16, 2018: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/29351859/structural-and-immunological-characterization-of-hydroxyl-radical-modified-human-igg-clinical-correlation-in-rheumatoid-arthritis
#7
Sidra Islam, Abdul Rouf Mir, Mir Yasir Arfat, Farzana Khan, Masihuz Zaman, Asif Ali, Moinuddin
Structural alterations in proteins under oxidative stress have been widely implicated in the immuno-pathology of various disorders. This study has evaluated the extent of damage in the conformational characteristics of IgG by hydroxyl radical (OH) and studied its implications in the immuno-pathology of rheumatoid arthritis (RA). Using various biophysical and biochemical techniques, changes in aromatic microenvironment of the IgG and the protein aggregation became evident after treatment with OH. The SDS-PAGE study confirmed the protein aggregation while far ultraviolet circular dichroism spectroscopy (Far-UV CD) and fourier transform infrared spectroscopy (FTIR) inferred towards the alterations in secondary structure of IgG under OH stress...
January 10, 2018: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
https://www.readbyqxmd.com/read/29351321/methylglyoxal-produces-more-changes-in-biochemical-and-biophysical-properties-of-human-igg-under-high-glucose-compared-to-normal-glucose-level
#8
Mohd Adnan Khan, Zarina Arif, Mohd Asad Khan, Moinuddin, Khursheed Alam
Hyperglycaemia triggers increased production of methylglyoxal which can cause gross modification in proteins' structure vis-a-vis function though advanced glycation end products (AGEs). The AGEs may initiate vascular and nonvascular pathologies. In this study, we have examined the biochemical and biophysical changes in human IgG under normal and high glucose after introducing methylglyoxal into the assay mixture. This non-enzymatic reaction mainly engaged lysine residues as indicated by TNBS results. The UV results showed hyperchromicity in modified-IgG samples while fluorescence data supported AGEs formation during the course of reaction...
2018: PloS One
https://www.readbyqxmd.com/read/29351282/a-four-component-model-of-the-action-potential-in-mouse-detrusor-smooth-muscle-cell
#9
Mithun Padmakumar, Keith L Brain, John S Young, Rohit Manchanda
BACKGROUND AND HYPOTHESIS: Detrusor smooth muscle cells (DSMCs) of the urinary bladder are electrically connected to one another via gap junctions and form a three dimensional syncytium. DSMCs exhibit spontaneous electrical activity, including passive depolarizations and action potentials. The shapes of spontaneous action potentials (sAPs) observed from a single DSM cell can vary widely. The biophysical origins of this variability, and the precise components which contribute to the complex shapes observed are not known...
2018: PloS One
https://www.readbyqxmd.com/read/29350433/amino-group-of-salicylic-acid-exhibits-enhanced-inhibitory-potential-against-insulin-amyloid-fibrillation-with-protective-aptitude-toward-amyloid-induced-cytotoxicity
#10
Masihuz Zaman, Mohsin Vahid Khan, Syed Mohammad Zakariya, Saima Nusrat, Syed Mustapha Meeran, Parvez Alam, Mohammad Rehan Ajmal, Wahiduzzaman Wahiduzzaman, Yasser E Shahein, Amira M Abouelella, Rizwan Hasan Khan
Protein misfolding and aggregation lead to amyloid generation that in turn may induce cell membrane disruption and leads to cell apoptosis. In an effort to prevent or treat amyloidogenesis, large number of studies has been paying attention on breakthrough of amyloid inhibitors. In the present work, we aim to access the effect of two drugs, that is, acetylsalicylic acid and 5-amino salicylic acid on insulin amyloids by using various biophysical, imaging, cell viability assay, and computational approaches. We established that both drugs reduce the turbidity, light scattering and fluorescence intensity of amyloid indicator dye thioflavin T...
December 11, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29347667/minimal-model-of-directed-cell-motility-on-patterned-substrates
#11
Matthew S Mizuhara, Leonid Berlyand, Igor S Aranson
Crawling cell motility is vital to many biological processes such as wound healing and the immune response. Using a minimal model we investigate the effects of patterned substrate adhesiveness and biophysical cell parameters on the direction of cell motion. We show that cells with low adhesion site formation rates may move perpendicular to adhesive stripes while those with high adhesion site formation rates results in motility only parallel to the substrate stripes. We explore the effects of varying the substrate pattern geometry and the strength of actin polymerization on the directionality of the crawling cell...
November 2017: Physical Review. E
https://www.readbyqxmd.com/read/29346777/prrt2-regulates-synaptic-fusion-by-directly-modulating-snare-complex-assembly
#12
Jeff Coleman, Ouardane Jouannot, Sathish K Ramakrishnan, Maria N Zanetti, Jing Wang, Vincenzo Salpietro, Henry Houlden, James E Rothman, Shyam S Krishnakumar
Mutations in proline-rich transmembrane protein 2 (PRRT2) are associated with a range of paroxysmal neurological disorders. PRRT2 predominantly localizes to the pre-synaptic terminals and is believed to regulate neurotransmitter release. However, the mechanism of action is unclear. Here, we use reconstituted single vesicle and bulk fusion assays, combined with live cell imaging of single exocytotic events in PC12 cells and biophysical analysis, to delineate the physiological role of PRRT2. We report that PRRT2 selectively blocks the trans SNARE complex assembly and thus negatively regulates synaptic vesicle priming...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29346724/structural-and-biophysical-characterization-of-human-extl3-domain-organisation-glycosylation-and-solution-structure
#13
Wael Awad, Sven Kjellstrom, Gabriel Svensson Birkedal, Katrin Mani, Derek Thomas Logan
Heparan sulfate proteoglycans are proteins substituted with one or more heparan sulfate (HS) polysaccharides, found in abundance at cell surfaces. HS chains influence the activity of many biologically important molecules involved in cellular communication and signaling. The exostosin (EXT) proteins are glycosyltransferases in the Golgi apparatus that assemble HS chains on HSPGs. The EXTL3 enzyme mainly works as an initiator in HS biosynthesis. In this work, human lumenal N-glycosylated EXTL3 (EXTL3ΔN) was cloned, expressed in human embryonic kidney cells and purified...
January 18, 2018: Biochemistry
https://www.readbyqxmd.com/read/29346028/biophysics-model-of-heavy-ion-degradation-of-neuron-morphology-in-mouse-hippocampal-granular-cell-layer-neurons
#14
Murat Alp, Francis A Cucinotta
Exposure to heavy-ion radiation during cancer treatment or space travel may cause cognitive detriments that have been associated with changes in neuron morphology and plasticity. Observations in mice of reduced neuronal dendritic complexity have revealed a dependence on radiation quality and absorbed dose, suggesting that microscopic energy deposition plays an important role. In this work we used morphological data for mouse dentate granular cell layer (GCL) neurons and a stochastic model of particle track structure and microscopic energy deposition (ED) to develop a predictive model of high-charge and energy (HZE) particle-induced morphological changes to the complex structures of dendritic arbors...
January 18, 2018: Radiation Research
https://www.readbyqxmd.com/read/29345991/collapse-transitions-of-proteins-and-the-interplay-among-backbone-sidechain-and-solvent-interactions
#15
Alex S Holehouse, Rohit V Pappu
Proteins can collapse into compact globules or form expanded, solvent-accessible, coil-like conformations. Additionally, they can fold into well-defined three-dimensional structures or remain partially or entirely disordered. Recent discoveries have shown that the tendency for proteins to collapse or remain expanded is not intrinsically coupled to their ability to fold. These observations suggest that proteins do not have to form compact globules in aqueous solutions. They can be intrinsically disordered, collapsed, or expanded, and even form well-folded, elongated structures...
January 18, 2018: Annual Review of Biophysics
https://www.readbyqxmd.com/read/29345990/imaging-mrna-in-vivo-from-birth-to-death
#16
Evelina Tutucci, Nathan M Livingston, Robert H Singer, Bin Wu
RNA is the fundamental information transfer system in the cell. The ability to follow single messenger RNAs (mRNAs) from transcription to degradation with fluorescent probes gives quantitative information about how the information is transferred fromDNAto proteins. This review focuses on the latest technological developments in the field of single-mRNA detection and their usage to study gene expression in both fixed and live cells. By describing the application of these imaging tools, we follow the journey of mRNA from transcription to decay in single cells, with single-molecule resolution...
January 18, 2018: Annual Review of Biophysics
https://www.readbyqxmd.com/read/29345989/assembly-of-copi-and-copii-vesicular-coat-proteins-on-membranes
#17
Julien Béthune, Felix T Wieland
In eukaryotes, distinct transport vesicles functionally connect various intracellular compartments. These carriers mediate transport of membranes for the biogenesis and maintenance of organelles, secretion of cargo proteins and peptides, and uptake of cargo into the cell. Transport vesicles have distinct protein coats that assemble on a donor membrane where they can select cargo and curve the membrane to form a bud. A multitude of structural elements of coat proteins have been solved by X-ray crystallography...
January 18, 2018: Annual Review of Biophysics
https://www.readbyqxmd.com/read/29345988/measuring-entropy-in-molecular-recognition-by-proteins
#18
A Joshua Wand, Kim A Sharp
Molecular recognition by proteins is fundamental to the molecular basis of biology. Dissection of the thermodynamic landscape governing protein-ligand interactions has proven difficult because determination of various entropic contributions is quite challenging. Nuclear magnetic resonance relaxation measurements, theory, and simulations suggest that conformational entropy can be accessed through a dynamical proxy. Here, we review the relationship between measures of fast side-chain motion and the underlying conformational entropy...
January 18, 2018: Annual Review of Biophysics
https://www.readbyqxmd.com/read/29345922/efficient-fusion-at-neutral-ph-by-human-immunodeficiency-virus-gp41-trimers-containing-the-fusion-peptide-and-transmembrane-domain
#19
Shuang Liang, Punsisi Ratnayake, Craig Keinath, Lihui Jia, Robert Wolfe, Ahinsa Ranaweera, David P Weliky
Human immunodeficiency virus (HIV) is membrane-enveloped and an initial infection step is joining/fusion of viral and cell membranes. This step is catalyzed by gp41 which is a single-pass integral viral membrane protein. The protein contains a ~170-residue ectodomain located outside the virus that is important for fusion, and includes the fusion peptide (FP), N-helix, loop, C-helix, and viral membrane-proximal external region (MPER). The virion initially has non-covalent complexes between three gp41 ectodomains and three gp120 proteins...
January 18, 2018: Biochemistry
https://www.readbyqxmd.com/read/29345503/effectiveness-of-the-biophysical-barriers-to-the-peridural-fibrosis-in-rat-laminectomy-model
#20
Ibrahim Akkurt, Bulent Bakar, Gungor Cagdas Dincel, Fatma Azize Budak Yıldıran, Mustafa Ogden, Egemen Nursoy, Elif Sari
PURPOSE: Peridural fibrosis which could occur after the spinal surgery could adhere neural tissue closely and may cause to neural entrapment symptoms and require surgical reintervention. AIM OF THE STUDY: Present study was designed to reduce occurrence of peridural fibrosis in rat laminectomy model by using biophysical barriers called hyaluronic acid (HAS) dural barrier, activated polyethylene glycol and polyethylene imine (PEG) dural barrier, and platelet-rich plasma (PRP)...
January 18, 2018: Journal of Investigative Surgery: the Official Journal of the Academy of Surgical Research
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