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Archives of Biochemistry and Biophysics

Katalin Uray, Malcolm V Pimm, Ferenc Hudecz
In order to establish structure-function relationship for the design of a new group of oligopeptide antigen-macromolecule conjugate, multiple copies of mucin-1 B-cell epitope peptide, APDTRPAPG were conjugated with branched chain polymeric polypeptides possessing poly[L-Lys] backbone. By the synthesis, radiolabeling (125 I) and in vivo treatment of BALB/c mice with epitope conjugates containing Xi K/XAK type carrier, where X = Glu (Ei K or EAK) or Leu (LAK), the influence of the polypeptide structure on the blood clearance profile and on tissue distribution profile concerning the epitope delivery to relevant organs (e...
February 8, 2019: Archives of Biochemistry and Biophysics
Francesco Simone Ruggeri, Tomas Šneideris, Michele Vendruscolo, Tuomas P J Knowles
The development of atomic force microscopy (AFM) has opened up a wide range of novel opportunities in nanoscience and new modalities of observation in complex biological systems. AFM imaging has been widely employed to resolve the complex and heterogeneous conformational states involved in protein aggregation at the single molecule scale and shed light onto the molecular basis of a variety of human pathologies, including neurodegenerative disorders. The study of individual macromolecules at nanoscale, however, remains challenging, especially when fully quantitative information is required...
February 8, 2019: Archives of Biochemistry and Biophysics
Reza Yekta, Gholamreza Dehghan, Samaneh Rashtbari, Leila Sadeghi, Behzad Baradaran, Nader Sheibani, Ali A Moosavi-Movahedi
Water molecules play a vital role in efficient drug binding to its target. Thiazolidinediones (TZDs), a class of anti-diabetic drugs, are widely used for treatment of type 2 diabetes mellitus. In the present study, the possible contribution of water molecules to the binding of TZDs to catalase, a potential target in the liver, was investigated by different experimental and theoretical methods. These studies indicated that TZDs could significantly improve the catalase catalytic function with a significant contribution from water molecules...
February 6, 2019: Archives of Biochemistry and Biophysics
Maryam Ghasemitarei, Maksudbek Yusupov, Jamoliddin Razzokov, Babak Shokri, Annemie Bogaerts
Extracellular cystine (CYC) uptake by xC- antiporter is important for the cell viability. Especially in cancer cells, the upregulation of xC- activity is observed, which protects these cells from intracellular oxidative stress. Hence, inhibition of the CYC uptake may eventually lead to cancer cell death. Up to now, the molecular level mechanism of the CYC uptake by xC- antiporter has not been studied in detail. In this study, we applied several different simulation techniques to investigate the transport of CYC through xCT, the light subunit of the xC- antiporter, which is responsible for the CYC and glutamate translocation...
February 6, 2019: Archives of Biochemistry and Biophysics
Alexis Díaz-Vegas, Verónica Eisner, Enrique Jaimovich
Mitochondria represent the main source of ATP in skeletal muscle and mitochondria activity increases after muscle fiber depolarization. The regulation of mitochondrial function during contraction in skeletal muscle, however, is poorly understood. Skeletal muscle has a particular distribution of mitochondria where three distinct populations can be recognized. The most studied populations are the ones positioned deep into the myofibers between the myofibrils (intermyofibrillar mitochondria), and that located immediately beneath sarcolemma (subsarcolemmal mitochondria); a less studied population locates covering the myonuclei, as a continuation of the subsarcolemmal population...
February 1, 2019: Archives of Biochemistry and Biophysics
Wieslawa Jarmuszkiewicz, Adam Szewczyk
Energy homeostasis in mitochondria is vital for proper muscle cell function. In this review we will focus on cardiac and skeletal muscle energy-dissipating systems, i.e., mitochondrial potassium channels and uncoupling proteins. Despite the molecular differences between these proteins both of them may regulate the generation of reactive oxygen species. Hence, they can both modulate pro-life and -death signaling in response to the needs of the muscle cell. Certain mitochondrial potassium channels (such as the ATP-regulated and large conductance calcium-activated mitochondrial potassium channels) and uncoupling proteins may be regulated in a similar manner suggesting that both are part of the energy-dissipating hub in muscle mitochondria...
February 1, 2019: Archives of Biochemistry and Biophysics
Panagiota S Georgoulia, Nicholas M Glykos
The application of molecular dynamics simulations to study the folding and dynamics of peptides has attracted a lot of interest in the last couple of decades. Following the successful prediction of the folding of several proteins using molecular simulation, foldable peptides emerged as a favourable system mainly due to their application in improving protein structure prediction methods and in drug design studies. However, their performance is inherently linked to the accuracy of the empirical force fields used in the simulations, whose optimisation and validation is of paramount importance...
January 31, 2019: Archives of Biochemistry and Biophysics
Lillian Truong, Yun-Min Zheng, Yong-Xiao Wang
Rieske iron-sulfur protein (RISP) is a catalytic subunit of the complex III in the mitochondrial electron transport chain. Studies for years have revealed that RISP is essential for the generation of intracellular reactive oxygen species (ROS) via delicate signaling pathways associated with many important molecules such as protein kinase C-ε, NADPH oxidase, and ryanodine receptors. More significantly, mitochondrial RISP-mediated ROS production has been implicated in the development of hypoxic pulmonary vasoconstriction, leading to pulmonary hypertension, right heart failure, and death...
January 30, 2019: Archives of Biochemistry and Biophysics
Charles S Chung
Movement of the myocardium can modify organ-level cardiac function and its molecular (crossbridge) mechanisms. This motion, which is defined by myocardial strain and strain rate (muscle shortening, lengthening, and the speed of these movements), occurs throughout the cardiac cycle, including during isovolumic periods. This review highlights how the left ventricular myocardium moves throughout the cardiac cycle, how muscle mechanics experiments provide insight into the regulation of forces used to move blood in and out of the left ventricle, and its impact on (and regulation by) crossbridge and sarcomere kinetics...
January 30, 2019: Archives of Biochemistry and Biophysics
Zoltán Szekanecz, Szilvia Szamosi, Gergő E Kovács, Elek Kocsis, Szilvia Benkő
The NLRP3 inflammasome is implicated in the processing of the pro-inflammatory cytokine interleukin 1β. Inflammatory disorders associated with the activation of the NLRP3 inflammasome - IL-1 axis are termed autoinflammatory diseases. Gout is an autoinflammatory disease, which is triggered by the deposition of monosodium urate crystals of precipitated uric acid. It is characterized by recurrent attacks of inflammation due to the activation of phagocytic cells that try to clear the crystals. NLRP3 inflammasome-mediated IL-1β production plays a key role in the manifestation of the disease...
January 30, 2019: Archives of Biochemistry and Biophysics
David Pantoja-Uceda, José L Neira, Lellys M Contreras, Christa A Manton, Danny R Welch, Bruno Rizzuti
BRMS1 is a 246-residue-long protein belonging to the family of metastasis suppressors. It is a predominantly nuclear protein, although it can also function in the cytoplasm. At its C terminus, it has a region that is predicted to be a nuclear localization sequence (NLS); this region, NLS2, is necessary for metastasis suppression. We have studied in vitro and in silico the conformational preferences in aqueous solution of a peptide (NLS2-pep) that comprises the NLS2 of BRMS1, to test whether it has a preferred conformation that could be responsible for its function...
January 29, 2019: Archives of Biochemistry and Biophysics
Kalkena Sivanesam, Niels Andersen
Amyloid fibril formation has long been studied because of the variety of proteins that are capable of adopting this structure despite sharing little sequence homology. This makes amyloid fibrils a challenging focus for inhibition studies because the peptides and proteins that form amyloid fibrils cannot be targeted based on a sequence motif. Most peptide inhibitors that target specific amyloidogenic proteins rely heavily on sequence recognition to ensure that the inhibitory peptide is able to bind its target...
January 29, 2019: Archives of Biochemistry and Biophysics
Luis Rivas, Verónica Rojas
Parasites are scarcely addressed target for antimicrobial peptides despite their big impact in health and global economy. The notion of antimicrobial peptides is frequently associated to the innate immune defense of vertebrates and invertebrate vectors, as the ultimate recipients of the parasite infection. These antiparasite peptides are produced by ribosomal synthesis, with few post-translational modifications, and their diversity come mostly from their amino acid sequence. For many of them permeabilization of the cell membrane of the targeted pathogen is crucial for their microbicidal mechanism...
January 29, 2019: Archives of Biochemistry and Biophysics
Tamsila Parveen, M Kamran, M Qaiser Fatmi
Mesophilic enzymes are among the most frequently used biocatalysts, however, psychrophilic enzymes are crucially important for their use in heat-sensitive reactions. How enzymes can work efficiently at various range of temperatures is an interesting subject for researchers, and yet it is very least explored. The structural and dynamical behavior of psychrophilic enzymes and their thermostability at various temperatures can help to understand the mechanism and function at molecular level, and for this purpose the ligand-free α-subunit of Shewanella frigidimarina's tryptophan synthase (Sf-TRPS) in isolated monomeric and in hetero-αβ-dimeric states was subjected to molecular dynamics (MD) simulations study...
January 28, 2019: Archives of Biochemistry and Biophysics
Nikola Kenjic, Matthew R Hoag, Garrett C Moraski, Carol A Caperelli, Graham R Moran, Audrey L Lamb
The hydroxyornithine transformylase from Pseudomonas aeruginosa is known by the gene name pvdF, and has been hypothesized to use N10 -formyltetrahydrofolate (N10 -fTHF) as a co-substrate formyl donor to convert N5 -hydroxyornithine (OHOrn) to N5 -formyl- N5 -hydroxyornithine (fOHOrn). PvdF is in the biosynthetic pathway for pyoverdin biosynthesis, a siderophore generated under iron-limiting conditions that has been linked to virulence, quorum sensing and biofilm formation. The structure of PvdF was determined by X-ray crystallography to 2...
January 25, 2019: Archives of Biochemistry and Biophysics
Sergio De la Fuente, Shey-Shing Sheu
In adult cardiomyocytes, T-tubules, junctional sarcoplasmic reticulum (jSR), and mitochondria juxtapose each other and form a unique and highly repetitive functional structure along the cell. The close apposition between jSR and mitochondria creates high Ca2+ microdomains at the contact sites, increasing the efficiency of the excitation-contraction-bioenergetics coupling, where the Ca2+ transfer from SR to mitochondria plays a critical role. The SR-mitochondria contacts are established through protein tethers, with mitofusin 2 the most studied SR-mitochondrial "bridge", albeit controversial...
January 24, 2019: Archives of Biochemistry and Biophysics
Brandon J Biesiadecki, Margaret V Westfall
Signaling complexes targeting the myofilament are essential in modulating cardiac performance. A central target of this signaling is cardiac troponin I (cTnI) phosphorylation. This review focuses on cTnI phosphorylation as a model for myofilament signaling, discussing key gaps and future directions towards understanding complex myofilament modulation of cardiac performance. Human heart cTnI is phosphorylated at 14 sites, giving rise to a complex modulatory network of varied functional responses. For example, while classical Ser23/24 phosphorylation mediates accelerated relaxation, protein kinase C phosphorylation of cTnI serves as a brake on contractile function...
January 23, 2019: Archives of Biochemistry and Biophysics
Jessica L Cao, Stephanie M Adaniya, Michael W Cypress, Yuta Suzuki, Yoichiro Kusakari, Bong Sook Jhun, Jin O-Uchi
Recent discoveries of the molecular identity of mitochondrial Ca2+ influx/efflux mechanisms have placed mitochondrial Ca2+ transport at center stage in views of cellular regulation in various cell-types/tissues. Indeed, mitochondria in cardiac muscles also possess the molecular components for efficient uptake and extraction of Ca2+ . Over the last several years, multiple groups have taken advantage of newly available molecular information about these proteins and applied genetic tools to delineate the precise mechanisms for mitochondrial Ca2+ handling in cardiomyocytes and its contribution to excitation-contraction/metabolism coupling in the heart...
January 23, 2019: Archives of Biochemistry and Biophysics
Dinesh Babu, Saifur R Khan, Nutan Srivastava, Lindsey Yeon Kyoung Suh, Andrew G Morgan, Naif Aljuhani, Richard P Fahlman, Arno G Siraki
Isoniazid (INH) is one of the oldest drugs for the treatment of tuberculosis (TB) and is of continual clinical and research interest. The aim of the current study is to investigate the ability of INH to induce monocyte differentiation and the underlying signaling pathway involved in this phenomenon using HL-60 cells. In this study, HL-60 cells were treated with different non-cytotoxic concentrations of INH or vitamin D (a well-known inducer of monocytic differentiation) to determine key functional changes in the phenotype of these cells using several biochemical and cytobiological experiments...
January 22, 2019: Archives of Biochemistry and Biophysics
Jingsong Zhou, Ang Li, Xuejun Li, Jianxun Yi
Amyotrophic lateral sclerosis (ALS) is a devastating neuromuscular disease characterized by motor neuron loss and prominent skeletal muscle wasting. Despite more than one hundred years of research efforts, the pathogenic mechanisms underlying neuromuscular degeneration in ALS remain elusive. While the death of motor neuron is a defining hallmark of ALS, accumulated evidences suggested that in addition to being a victim of motor neuron axonal withdrawal, the intrinsic skeletal muscle degeneration may also actively contribute to ALS disease pathogenesis and progression...
January 22, 2019: Archives of Biochemistry and Biophysics
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