Biomedical potential of chitosan‑silver nanoparticles with special reference to antioxidant, antibacterial, hemolytic and in vivo cutaneous wound healing effects
Publication date: Available online 16 October 2018Source: Biochimica et Biophysica Acta (BBA) - General SubjectsAuthor(s): Sawssen Hajji, Sameh Ben Khedir, Ibtissem Hamza-Mnif, Marwa Hamdi, Ines Jedidi, Rim Kallel, Sami Boufi, Moncef NasriAbstractThe aim of the present study was to prepare chitosan-PVA‑silver nanoparticles (CS-AgNPs) through green method. Chitosan and PVA polymers acted as stabilizing agents. DLS and TEM analyses showed that CS-AgNPs were homogeneously dispersed in matrix with an average size of 190–200 nm. The CS-AgNPs were tested for their antioxidant and antibacterial properties and the result...
Source: Biochimica et Biophysica Acta (BBA) General Subjects - October 17, 2018 Category: Biochemistry Source Type: research

Catechin-Mediated Restructuring of a Bacterial Toxin Inhibits Activity
Conclusions: These results demonstrate that the catechins inhibit LtxA activity by altering its structure to prevent interaction with specific molecules present on the host cell surface. General Significance: Galloylated catechins modify protein toxin structure, inhibiting the toxin from binding to the requisite molecules on the host cell surface.Graphical abstract (Source: Biochimica et Biophysica Acta (BBA) General Subjects)
Source: Biochimica et Biophysica Acta (BBA) General Subjects - October 17, 2018 Category: Biochemistry Source Type: research

Interplay of Extracellular Vesicles and other players in Cerebral Malaria Pathogenesis
Conclusions.Microvesicles and exosomes are implicated in cerebral malaria pathogenesis, in the modulation of host immunity to Plasmodium, and in cell-cell communication. Blocking their production is protective in models of cerebral malaria, both in vivo and in vitro.General Significance.While anti-malarial treatments exist to combat Plasmodium infections, increasing drug resistance presents a major challenge. In order to improve diagnosis and treatment outcomes, further research is required to better appreciate extracellular vesicle involvement in cerebral malaria. (Source: Biochimica et Biophysica Acta (BBA) General Subjects)
Source: Biochimica et Biophysica Acta (BBA) General Subjects - October 17, 2018 Category: Biochemistry Source Type: research

Editorial Board
Publication date: December 2018Source: Biochimica et Biophysica Acta (BBA) - General Subjects, Volume 1862, Issue 12Author(s): (Source: Biochimica et Biophysica Acta (BBA) General Subjects)
Source: Biochimica et Biophysica Acta (BBA) General Subjects - October 17, 2018 Category: Biochemistry Source Type: research

Biophysical Simulations and Structure-Based Modeling of Residue Interaction Networks in the Tumor Suppressor Proteins Reveal Functional Role of Cancer Mutation Hotspots in Molecular Communication
Publication date: Available online 16 October 2018Source: Biochimica et Biophysica Acta (BBA) - General SubjectsAuthor(s): Gennady M. VerkhivkerAbstractIn the current study, we have combined molecular simulations and energetic analysis with dynamics-based network modeling and perturbation response scanning to determine molecular signatures of mutational hotspot residues in the p53, PTEN, and SMAD4 tumor suppressor proteins. By examining structure, energetics and dynamics of these proteins, we have shown that inactivating mutations preferentially target a group of structurally stable residues that play a fundamental role in...
Source: Biochimica et Biophysica Acta (BBA) General Subjects - October 16, 2018 Category: Biochemistry Source Type: research

Insulin adsorption onto zinc oxide nanoparticle mediates conformational rearrangement into amyloid-prone structure with enhanced cytotoxic propensity
ConclusionsThe presence of ZnONP interface enhances fibrillation of insulin at physiological pH by providing a favourable template for the nucleation and growth of insulin amyloids.General significance.The studied protein-nanoparticle system from protein conformational dynamics point of view throws caution over nanoparticle use in biological applications, especially in vivo applications, considering the amyloidosis a very slow but non-curable degenerative disease.Graphical abstract (Source: Biochimica et Biophysica Acta (BBA) General Subjects)
Source: Biochimica et Biophysica Acta (BBA) General Subjects - October 12, 2018 Category: Biochemistry Source Type: research

Boron inhibits apoptosis in hyperapoptosis condition: Acts by stabilizing the mitochondrial membrane and inhibiting matrix remodeling
In this study, boron is reported to inhibit apoptosis in hyperapoptosis conditions as demonstrated in a model of hyperapoptosis. Boron is a metalloid which is present in food in small amounts and is suggested here to inhibit apoptosis by stabilizing the mitochondrial membrane structure, thus preventing matrix remodeling and the release of cytochrome c, an apoptosis-inducer protein from the mitochondrion. The protective effect was assessed by measuring the changes in mitochondrial membrane potential, the levels of cytochrome c and downstream activation of caspase 3, besides phosphatidylserine exposure on the cell surface an...
Source: Biochimica et Biophysica Acta (BBA) General Subjects - October 10, 2018 Category: Biochemistry Source Type: research

MV-mimicking Micelles Loaded with PEG-Serine-ACP Nanoparticles to Achieve Biomimetic Intra/Extra Fibrillar Mineralization of Collagen In Vitro
In this study, high-concentration serine was used to stabilize the amorphous calcium phosphate (S-ACP), which was subsequently mixed with polyethylene glycol (PEG) to form PEG-S-ACP nanoparticles. The nanoparticles were loaded in the polysorbate 80 micelle through a micelle self-assembly process in an aqueous environment. This MVs–mimicking model is referred to as the PEG-S-ACP/micelle model. By adjusting the pH and surface tension of the PEG-S-ACP/micelle, two forms of minerals (crystalline mineral nodules and ACP nanoparticles) were released to achieve the extrafibrillar and intrafibrillar mineralization, respectiv...
Source: Biochimica et Biophysica Acta (BBA) General Subjects - October 10, 2018 Category: Biochemistry Source Type: research

Long-chain polyphosphate in osteoblast matrix vesicles: Enrichment and inhibition of mineralization
ConclusionPolyP is highly enriched in matrix vesicles and can inhibit apatite formation. PolyP may be hydrolysed to phosphate for further mineralization in the extracellular matrix.General significance: PolyP is a unique yet underappreciated macromolecule which plays a critical role in extracellular mineralization in matrix vesicles. (Source: Biochimica et Biophysica Acta (BBA) General Subjects)
Source: Biochimica et Biophysica Acta (BBA) General Subjects - October 10, 2018 Category: Biochemistry Source Type: research

Methylation of Selenocysteine catalysed by Thiopurine S-Methyltransferase
ConclusionsThe present study provides evidence on in vitro methylation of Sec by rTPMT in a SAM-dependant manner.General Significance.Our results suggest novel role of TPMT and demonstrate new insights into enzymatic modifications of the 21st amino acid.Graphical abstract (Source: Biochimica et Biophysica Acta (BBA) General Subjects)
Source: Biochimica et Biophysica Acta (BBA) General Subjects - October 9, 2018 Category: Biochemistry Source Type: research

Deinococcus radiodurans' SRA-HNH domain containing protein Shp (Dr1533) is involved in faithful genome inheritance maintenance following DNA damage
ConclusionsThe SRA-HNH containing protein Shp binds to and cuts 5mC DNA, and unmethylated DNA in a Mn2+ dependent manner, and might be involved in faithful genome inheritance maintenance following DNA damage.General significanceOur results provide evidence for a potential role of DR Shp protein for genome integrity maintenance, following DNA double strand breaks induced by genotoxic agents. (Source: Biochimica et Biophysica Acta (BBA) General Subjects)
Source: Biochimica et Biophysica Acta (BBA) General Subjects - October 9, 2018 Category: Biochemistry Source Type: research

Pancreatic cancer stem cell proliferation is strongly inhibited by diethyldithiocarbamate-copper complex loaded into hyaluronic acid decorated liposomes
ConclusionsThe obtained results show that the encapsulation of Cu(DDC)2 complex in HA decorated liposomes strongly increases its anti-proliferative activity on pancreatic CSCs.General significanceThis paper describes for the first time the use of HA decorated liposomes containing Cu(DDC)2 against pancreatic CSCs and opens the way to the development of nanomedicine based CSC-targeted therapeutic approaches.Graphical abstract (Source: Biochimica et Biophysica Acta (BBA) General Subjects)
Source: Biochimica et Biophysica Acta (BBA) General Subjects - October 6, 2018 Category: Biochemistry Source Type: research

Atomistic mechanism of the constitutive activation of PDGFRA via its transmembrane domain
Publication date: Available online 22 September 2018Source: Biochimica et Biophysica Acta (BBA) - General SubjectsAuthor(s): Anton A. Polyansky, Eduard V. Bocharov, Amélie I. Velghe, Andrey S. Kuznetsov, Olga V. Bocharova, Anatoly S. Urban, Alexander S. Arseniev, Bojan Zagrovic, Jean-Baptiste Demoulin, Roman G. EfremovAbstractSingle-point mutations in the transmembrane (TM) region of receptor tyrosine kinases (RTKs) can lead to abnormal ligand-independent activation. We use a combination of computational modeling, NMR spectroscopy and cell experiments to analyze in detail the mechanism of how TM domains contribute t...
Source: Biochimica et Biophysica Acta (BBA) General Subjects - October 5, 2018 Category: Biochemistry Source Type: research

Pancreatic cancer stem cell proliferation is strongly inhibited by diethyldithiocarbamate‑copper complex loaded into hyaluronic acid decorated liposomes
ConclusionsThe obtained results show that the encapsulation of Cu(DDC)2 complex in HA decorated liposomes strongly increases its anti-proliferative activity on pancreatic CSCs.General significanceThis paper describes for the first time the use of HA decorated liposomes containing Cu(DDC)2 against pancreatic CSCs and opens the way to the development of nanomedicine based CSC-targeted therapeutic approaches.Graphical abstract (Source: Biochimica et Biophysica Acta (BBA) General Subjects)
Source: Biochimica et Biophysica Acta (BBA) General Subjects - October 5, 2018 Category: Biochemistry Source Type: research

ABC transporters as cancer drivers: Potential functions in cancer development
Publication date: Available online 27 September 2018Source: Biochimica et Biophysica Acta (BBA) - General SubjectsAuthor(s): Alice Domenichini, Aleksandra Adamska, Marco FalascaAbstractBackgroundABC transporters have attracted considerable attention for their function as drug transporters in a broad range of tumours and are therefore considered as major player in cancer chemoresistance. However, less attention has been focused on their potential role as active players in cancer development and progression.Scope of reviewThis review presents the evidence suggesting that ABC transporters might have a more active role in canc...
Source: Biochimica et Biophysica Acta (BBA) General Subjects - October 5, 2018 Category: Biochemistry Source Type: research

Modulating α-synuclein fibril formation using DNA tetrahedron nanostructures
Publication date: Available online 29 September 2018Source: Biochimica et Biophysica Acta (BBA) - General SubjectsAuthor(s): Wan Ki Yoo, Bum Han Ryu, Kyoung-Ran Kim, Ying Wang, Ly Thi Huong Luu Le, Jun Hyuck Lee, Kyeong Kyu Kim, Gergely Toth, Dae-Ro Ahn, T. Doohun KimAbstractThe small presynaptic protein α-synuclein (α-syn) is involved in the etiology of Parkinson's disease owing to its abnormal misfolding. To date, little information is known on the role of DNA nanostructures in the formation of α-syn amyloid fibrils. Here, the effects of DNA tetrahedrons on the formation of α-syn amyloid fibrils w...
Source: Biochimica et Biophysica Acta (BBA) General Subjects - October 5, 2018 Category: Biochemistry Source Type: research

Is CYP1B1 involved in the metabolism of dioxins in the pig?
Publication date: Available online 29 September 2018Source: Biochimica et Biophysica Acta (BBA) - General SubjectsAuthor(s): Tomasz Molcan, Sylwia Swigonska, Anna Nynca, Agnieszka Sadowska, Monika Ruszkowska, Karina Orlowska, Renata E. CiereszkoAbstract2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is the most difficult to biodegradate and the most toxic dioxin congener. Previously, we demonstrated in silico the ability of pig CYP1A1 to hydroxylate 2,7-dichlorodibenzo-p-dioxin (DiCDD), but not TCDD. To increase our knowledge concerning the low effectiveness of TCDD biodegradability, we analyzed in silico the binding selectivit...
Source: Biochimica et Biophysica Acta (BBA) General Subjects - October 5, 2018 Category: Biochemistry Source Type: research

Characterization of an RNase with two catalytic centers. Human RNase6 catalytic and phosphate-binding site arrangement favors the endonuclease cleavage of polymeric substrates
ConclusionsWe have identified the residues that participate in RNase6 second catalytic triad (His36/His39/Lys87) and secondary phosphate-binding sites. To note, residues His39 and Lys87 are unique within higher primates. The RNaseA/RNase6 side-by-side comparison correlates the presence of a dual active site in RNase6 with a favored endonuclease-type cleavage pattern.General significanceAn RNase dual catalytic and extended binding site arrangement facilitates the cleavage of polymeric substrates. This is the first report of the presence of two catalytic centers in a single monomer within the RNaseA superfamily.Graphical abs...
Source: Biochimica et Biophysica Acta (BBA) General Subjects - October 5, 2018 Category: Biochemistry Source Type: research

Targeting glutathione s-transferase p and its interactome with selenium compounds in cancer therapy
Publication date: Available online 2 October 2018Source: Biochimica et Biophysica Acta (BBA) - General SubjectsAuthor(s): D. Bartolini, P. Torquato, M. Piroddi, F. GalliAbstractThe glutathione (GSH) S-transferase family of detoxification and signalling proteins represents a major hub for the metabolism of Selenium-derived compounds. At the same time, these compounds can be used to modulate the expression and multiple activities of GSTs and other glutathione-dependent genes, that are important aspects in both the chemoprevention and therapy of drug-resistant cancers.In this context, the isoform GSTP-1 (GSTP) appears to play...
Source: Biochimica et Biophysica Acta (BBA) General Subjects - October 5, 2018 Category: Biochemistry Source Type: research

Widening the antimicrobial spectrum of esters of bicyclic amines: In vitro effect on gram-positive Streptococcus pneumoniae and gram-negative non-typeable Haemophilus influenzae biofilms
Publication date: Available online 5 October 2018Source: Biochimica et Biophysica Acta (BBA) - General SubjectsAuthor(s): Emma Roig-Molina, Mirian Domenech, María de Gracia Retamosa, Montserrat Nácher-Vázquez, Luis Rivas, Beatriz Maestro, Pedro García, Ernesto García, Jesús M. SanzAbstractAntibiotic resistance is a global current threat of increasing importance. Moreover, biofilms represent a medical challenge since the inherent antibiotic resistance of their producers demands the use of high doses of antibiotics over prolonged periods. Frequently, these therapeutic measures fail, ...
Source: Biochimica et Biophysica Acta (BBA) General Subjects - October 5, 2018 Category: Biochemistry Source Type: research

Identification of (4-(9H-fluoren-9-yl) piperazin-1-yl) methanone derivatives as falcipain 2 inhibitors active against Plasmodium falciparum cultures
Publication date: December 2018Source: Biochimica et Biophysica Acta (BBA) - General Subjects, Volume 1862, Issue 12Author(s): Jorge E. Hernández-González, Emir Salas-Sarduy, Luisa F. Hernández Ramírez, María J. Pascual, Diego E. Álvarez, Adriana Pabón, Vitor B.P. Leite, Pedro G. Pascutti, Pedro A. ValienteAbstractBackgroundFalcipain 2 (FP-2) is the hemoglobin-degrading cysteine protease of Plasmodium falciparum most extensively targeted to develop novel antimalarials. However, no commercial antimalarial drugs based on FP-2 inhibition are available yet due to the low selecti...
Source: Biochimica et Biophysica Acta (BBA) General Subjects - October 5, 2018 Category: Biochemistry Source Type: research

A noncanonical binding site of chloramphenicol revealed via molecular dynamics simulations
Publication date: December 2018Source: Biochimica et Biophysica Acta (BBA) - General Subjects, Volume 1862, Issue 12Author(s): G.I. Makarov, T.M. MakarovaAbstractChloramphenicol, an antibiotic belonging to the family of amphenicols, is an inhibitor of translation. On the basis of X–ray structural analysis of the binding of chloramphenicol to free bacterial ribosomes, the chloramphenicol action mechanism that consists in preventing the binding of aminoacyl-tRNA to the A–site of the large subunit of the ribosome was adopted. However, the known structures of chloramphenicol complexes with bacterial ribosomes poorl...
Source: Biochimica et Biophysica Acta (BBA) General Subjects - October 5, 2018 Category: Biochemistry Source Type: research

Insulin-like growth factor type I selectively binds to G-quadruplex structures
ConclusionsIGF-1 is demonstrated to selectively bind with G-quadruplex structures. The use of quadruplex-interactive ligands could modulate the binding of IGF-1 to G-quadruplexes.General significanceThis study provides us with a new perspective to understand the possible physiological relationship between IGF-1 and G-quadruplexes and also conveys a strategy to regulate the interaction between G-quadruplex DNA and proteins.Graphical abstractSchematic representation of the selective binding of IGF-1 for G-quadruplex structures (Source: Biochimica et Biophysica Acta (BBA) General Subjects)
Source: Biochimica et Biophysica Acta (BBA) General Subjects - October 5, 2018 Category: Biochemistry Source Type: research

Identification of amino acid residues critical for the B cell growth-promoting activity of HIV-1 matrix protein p17 variants
ConclusionsThe molecular reasons for the proliferative activity of vp17s, compared to refp17, relies on the exposure of a functional epitope capable of activating Akt.General significanceOur findings pave the way for identifying the receptor(s) responsible for B cell proliferation and offer new opportunities to identify novel treatment strategies in combating HIV-related NHL. (Source: Biochimica et Biophysica Acta (BBA) General Subjects)
Source: Biochimica et Biophysica Acta (BBA) General Subjects - October 5, 2018 Category: Biochemistry Source Type: research

Circulating small non-coding RNAs provide new insights into vitamin K nutrition and reproductive physiology in teleost fish
ConclusionsVK supplementation improves fish gonad maturation and sperm quality, suggesting an unexpected and complex regulation of the nutritional status and reproductive performance through circulating sncRNAs.General significanceThe use of circulating sncRNAs as reliable and less-invasive physiological biomarkers in fish nutrition and reproduction has been unveiled. (Source: Biochimica et Biophysica Acta (BBA) General Subjects)
Source: Biochimica et Biophysica Acta (BBA) General Subjects - October 5, 2018 Category: Biochemistry Source Type: research

Genetically encoded fluorescent indicators for live cell pH imaging
Publication date: Available online 20 September 2018Source: Biochimica et Biophysica Acta (BBA) - General SubjectsAuthor(s): Vladimir I. Martynov, Alexey A. Pakhomov, Igor E. Deyev, Alexander G. PetrenkoAbstractBackgroundIntracellular pH underlies most cellular processes. There is emerging evidence of a pH-signaling role in plant cells and microorganisms. Dysregulation of pH is associated with human diseases, such as cancer and Alzheimer's disease.Scope of reviewIn this review, we attempt to provide a summary of the progress that has been made in the field during the past two decades. First, we present an overview of the c...
Source: Biochimica et Biophysica Acta (BBA) General Subjects - September 22, 2018 Category: Biochemistry Source Type: research

Dependence of HSP27 cellular level on protein kinase CK2 discloses novel therapeutic strategies
ConclusionBeing HSP27 involved in several pathological conditions, including protein conformational diseases (i.e Cystic Fibrosis) and cancer, the need of drugs to modulate its activity is growing and CK2-targeting could represent a new strategy to reduce cellular HSP27 level.General significanceThis study identifies CK2 as a molecular target to control HSP27 cellular expression. (Source: Biochimica et Biophysica Acta (BBA) General Subjects)
Source: Biochimica et Biophysica Acta (BBA) General Subjects - September 22, 2018 Category: Biochemistry Source Type: research

Structural and enzymatic properties of Ageritin, a novel metal-dependent ribotoxin-like protein with antitumor activity
Publication date: Available online 18 September 2018Source: Biochimica et Biophysica Acta (BBA) - General SubjectsAuthor(s): Alessia Ruggiero, Lucía García-Ortega, Sara Ragucci, Rosita Russo, Nicola Landi, Rita Berisio, Antimo Di MaroAbstractAgeritin has been recently described as the first ribotoxin-like from Basidiomycota division (mushroom Agrocybe aegerita) with known antitumor activity (BBA 2017, 1861: 1113-1121). By investigating structural, catalytic and binding properties, we demonstrate that Ageritin is a unique ribotoxin-like protein. Indeed, typical of the ribotoxin family, it shows the specific ri...
Source: Biochimica et Biophysica Acta (BBA) General Subjects - September 18, 2018 Category: Biochemistry Source Type: research

The physiological role of the free 20S proteasome in protein degradation: A critical review
Publication date: Available online 16 September 2018Source: Biochimica et Biophysica Acta (BBA) - General SubjectsAuthor(s): Marilene Demasi, Fernanda M. da CunhaAbstractBackgroundIt has been almost three decades since the removal of oxidized proteins by the free 20S catalytic unit of the proteasome (20SPT) was proposed. Since then, experimental evidence suggesting a physiological role of proteolysis mediated by the free 20SPT has being gathered.Scope of reviewExperimental data that favors the hypothesis of free 20SPT as playing a role in proteolysis are critically reviewed.Major conclusionsProtein degradation by the prote...
Source: Biochimica et Biophysica Acta (BBA) General Subjects - September 17, 2018 Category: Biochemistry Source Type: research

Protein topology determines substrate-binding mechanism in homologous enzymes
Publication date: Available online 12 September 2018Source: Biochimica et Biophysica Acta (BBA) - General SubjectsAuthor(s): Alejandra Herrera-Morande, Victor Castro-Fernández, Felipe Merino, Cesar Ramírez-Sarmiento, Francisco J. Fernández, M. Cristina Vega, Victoria GuixéAbstractDuring evolution, some homologs proteins appear with different connectivity between secondary structures (different topology) but conserving the tridimensional arrangement of them (same architecture). These events can produce two types of arrangements; circular permutation or non-cyclic permutations. The first one resul...
Source: Biochimica et Biophysica Acta (BBA) General Subjects - September 13, 2018 Category: Biochemistry Source Type: research

High-resolution atomic force microscopy visualization of metalloproteins and their complexes
ConclusionsGM-HOPG was shown to be a convenient substrate for AFM investigation of metalloproteins and their complexes. Direct AFM visualization of MPO-CP and LF-CP complexes, on the one hand, complements previous data obtained from the “bulk techniques” and, on the other hand, provides new insight into the ultrastructure of MPO-CP complexes.General significanceThe obtained results contribute to the better understanding of regulation of inflammation and oxidation stress mediated by collaborative action of the metalloproteins such as MPO, CP and LF.Graphical abstract (Source: Biochimica et Biophysica Acta (BBA) General Subjects)
Source: Biochimica et Biophysica Acta (BBA) General Subjects - September 13, 2018 Category: Biochemistry Source Type: research

Myrtenal-induced V-ATPase inhibition - A toxicity mechanism behind tumor cell death and suppressed migration and invasion in melanoma
ConclusionsThese data revealed the therapeutic potential of Myrtenal as inhibitor of melanoma progression proposing a mechanism of action by which once inhibited by this monoterpene the proton pumps fail to activate cancer-related differential electrochemical gradients and H+ fluxes across the tumor cell membranes, disrupting pH signatures inherent in tumor progression, resulting in reprogrammed cell death and metastasis inhibition.General significanceThe work represents a new mechanistic strategy for contention of melanoma, the most aggressive and deadly form of cutaneous neoplasm, and highlights Myrtenal, other related m...
Source: Biochimica et Biophysica Acta (BBA) General Subjects - September 12, 2018 Category: Biochemistry Source Type: research

Detection and quantitation of iron in ferritin, transferrin and labile iron pool (LIP) in cardiomyocytes using 55Fe and storage phosphorimaging
In this study, we have performed metabolic labeling of primary cultures of neonatal rat cardiomyocytes with radioactive iron coupled with separation of labeled iron-containing molecules by native electrophoresis followed by the detection and quantification of incorporated radioiron by storage phosphorimaging. For the radiolabeling we used a safe and convenient beta emitter 55Fe which enabled sensitive and simultaneous detection and quantitation of iron in cardiomyocyte ferritin, transferrin and the labile iron pool (LIP). The LIP is believed to represent potentially dangerous redox–active iron bound to uncharacterize...
Source: Biochimica et Biophysica Acta (BBA) General Subjects - September 11, 2018 Category: Biochemistry Source Type: research

Palmitoylation is a post-translational modification of Alix regulating the membrane organization of exosome-like small extracellular vesicles
ConclusionsWe propose that S-palmitoylation regulates the function of Alix in facilitating the interactions among extracellular vesicle-specific regulators and maintains the proper structural organization of exosome-like extracellular vesicle membranes.General SignificanceBeyond its biological relevance, our study also provides the means for a comprehensive structural characterization of EVs.Graphical abstract (Source: Biochimica et Biophysica Acta (BBA) General Subjects)
Source: Biochimica et Biophysica Acta (BBA) General Subjects - September 8, 2018 Category: Biochemistry Source Type: research

Metastable states of HYPK-UBA domain's seeds drive the dynamics of its own aggregation
Publication date: Available online 7 September 2018Source: Biochimica et Biophysica Acta (BBA) - General SubjectsAuthor(s): Debasish Kumar Ghosh, Abhishek Kumar, Akash RanjanAbstractProtein aggregation is a multi-step process that requires sequential structural transitions of monomers during their incorporation into oligomers. Such process involves the formation of various intermediate stages in protein structures. Seed-nucleation mediated oligomerization is observed in many aggregation-prone proteins. Understanding of the protein seed's structural features and mechanisms of its transition-state formation are important for...
Source: Biochimica et Biophysica Acta (BBA) General Subjects - September 8, 2018 Category: Biochemistry Source Type: research

Determinative factors in inhibition of aquaporin by different pharmaceuticals: Atomic scale overview by molecular dynamics simulation
Publication date: Available online 5 September 2018Source: Biochimica et Biophysica Acta (BBA) - General SubjectsAuthor(s): Vahid Fadaei Naeini, Masumeh Foroutan, Mina Maddah, Yves Rémond, Majid BaniassadiAbstractThe inhibition of water permeation through aquaporins by ligands of pharmaceutical compounds is considered as a method to control the cell lifetime. The inhibition of aquaporin 1 (AQP1) by bacopaside-I and torsemide, was explored and its atomistic nature was elucidated by molecular docking and molecular dynamics (MD) simulation collectively along with Poisson-Boltzmann surface area (PBSA) method. Docking re...
Source: Biochimica et Biophysica Acta (BBA) General Subjects - September 5, 2018 Category: Biochemistry Source Type: research

Loss of cytosolic Mg2+ binding sites in the Thermotoga maritima CorA Mg2+ channel is not sufficient for channel opening
Publication date: Available online 5 September 2018Source: Biochimica et Biophysica Acta (BBA) - General SubjectsAuthor(s): Thomas Kowatz, Michael E. MaguireAbstractThe CorA Mg2+ channel is a homopentamer with five-fold symmetry. Each monomer consists of a large cytoplasmic domain and two transmembrane helices connected via a short periplasmic loop. In the Thermotoga maritima CorA crystal structure, a Mg2+ is bound between D89 of one monomer and D253 of the adjacent monomer (M1 binding site). Release of Mg2+ from these sites has been hypothesized to cause opening of the channel. We generated mutants to disrupt Mg2+ interac...
Source: Biochimica et Biophysica Acta (BBA) General Subjects - September 5, 2018 Category: Biochemistry Source Type: research

In vitro Neurotoxicity of Salsolinol is Attenuated by the Presynaptic Protein α-Synuclein
ConclusionsInteraction of SALSO with aS leads to the formation of fibril-incompetent and innocuous adducts. SALSO toxicity is attenuated by aS monomer.SignificanceaS could exhibit a protective role against the neurotoxic effects of SALSO in dopaminergic neuron. (Source: Biochimica et Biophysica Acta (BBA) General Subjects)
Source: Biochimica et Biophysica Acta (BBA) General Subjects - September 4, 2018 Category: Biochemistry Source Type: research

Quantification of Kinetic Rate Constants for Transcytosis of Polymeric Nanoparticle through Blood-Brain Barrier
ConclusionsOur model results indicate that exocytosis (t12,exo=14.2h) of nanoparticles is seven fold slower to endocytosis (t12,endo=1.9h) suggesting that future studies should focus on enhancing the exocytosis process.General significance.This mathematical study will assist in designing new drug carriers to overcome the drug delivery problems in brain. Furthermore, we anticipate that this model will form the basis of future comprehensive models for drug transport across BBB. (Source: Biochimica et Biophysica Acta (BBA) General Subjects)
Source: Biochimica et Biophysica Acta (BBA) General Subjects - September 1, 2018 Category: Biochemistry Source Type: research

Nitric oxide reverses drug resistance by inhibiting ATPASE activity of p-glycoprotein in human multi-drug resistant cancer cells
ConclusionsThe reversal of drug resistance is due to inhibition of the ATPase activity by ●NO, resulting in enhancement of the drug accumulation in the MDR cells. Furthermore, DNA damage was not responsible for this reversal of adriamycin resistance. However, formation of adriamycin-dependent toxic free radical species and subsequent cellular damage may be responsible for the increased cytotoxicity of adriamycin by ●NO in NCI/ADR-RES cells.General Significance.Appropriately designed NO donors would be ideal for the treatment of P-gp-overexpressing tumors in the clinic. (Source: Biochimica et Biophysica Acta (BBA) General Subjects)
Source: Biochimica et Biophysica Acta (BBA) General Subjects - September 1, 2018 Category: Biochemistry Source Type: research

Nanobodies as novel therapeutic agents in envenomation
Conclusions.Nanobodies bind to their cognate target with high specificity and affinity, they can be produced in large quantities from microbial expression systems and are very robust even when challenged with harsh environmental conditions. Upon administering, they rapidly distribute throughout the body and seem to be well tolerated in humans posing low immunogenicity.General Significance.Scorpion and snake envenomation is a major issue in developing countries and nanobodies as a venom-neutralizing agent can be considered as a valuable and promising candidate in envenomation therapy. (Source: Biochimica et Biophysica Acta ...
Source: Biochimica et Biophysica Acta (BBA) General Subjects - August 31, 2018 Category: Biochemistry Source Type: research

Supramolecular zippers elicit interbilayer adhesion of membranes producing cell death
ConclusionsWe conclude that membrane adhesion induced by NAO stacking accounts for the supramolecular basis of its cytotoxicity.General significanceMitochondria are a potential target for cancer and gene therapies. The alteration of the mitochondrial structure by membrane remodeling agents able to form supramolecular assemblies via adhesion properties could be envisaged as a new therapeutic strategy.Graphical abstract (Source: Biochimica et Biophysica Acta (BBA) General Subjects)
Source: Biochimica et Biophysica Acta (BBA) General Subjects - August 31, 2018 Category: Biochemistry Source Type: research

Cloning and characterisation of the Equilibrative Nucleoside Transporter family of Trypanosoma cruzi: Ultra-high affinity and selectivity to survive in the intracellular niche
ConclusionsThe data appear to show that, surprisingly, T. cruzi has a preference for oxopurines over aminopurines and efficiently transports 2′-deoxypyrimidines. The T. cruzi ENTs display exceptionally high substrate affinity as an adaptation to their intracellular localisation.General significanceThis study reports the first cloning of T. cruzi purine and pyrimidine transporters, including the first gene encoding a pyrimidine-selective protozoan transporter. (Source: Biochimica et Biophysica Acta (BBA) General Subjects)
Source: Biochimica et Biophysica Acta (BBA) General Subjects - August 25, 2018 Category: Biochemistry Source Type: research

Structural properties of the peroxiredoxin AhpC2 from the hyperthermophilic eubacterium Aquifex aeolicus
This study provides novel insights into the structure and reaction mechanism of 1-Cys peroxiredoxins. (Source: Biochimica et Biophysica Acta (BBA) General Subjects)
Source: Biochimica et Biophysica Acta (BBA) General Subjects - August 25, 2018 Category: Biochemistry Source Type: research

Anti-cancer activities of Bharangin against breast cancer: Evidence for the role of NF-κB and lncRNAs
Publication date: Available online 24 August 2018Source: Biochimica et Biophysica Acta (BBA) - General SubjectsAuthor(s): Nikee Awasthee, Vipin Rai, Sumit S. Verma, K. Sajin Francis, Mangalam S. Nair, Subash C. GuptaAbstractBreast cancer remains one of the leading causes of cancer related deaths in women worldwide. Bharangin is a diterpenoid quinonemethide that has demonstrated therapeutic potential against leukemia, lymphoma, and multiple myeloma cells. Whether this diterpenoid exhibit activities against breast cancer cells and the underlying mechanism is largely unknown. Herein, we provide evidence that bharangin suppres...
Source: Biochimica et Biophysica Acta (BBA) General Subjects - August 25, 2018 Category: Biochemistry Source Type: research

Editorial Board
Publication date: November 2018Source: Biochimica et Biophysica Acta (BBA) - General Subjects, Volume 1862, Issue 11Author(s): (Source: Biochimica et Biophysica Acta (BBA) General Subjects)
Source: Biochimica et Biophysica Acta (BBA) General Subjects - August 22, 2018 Category: Biochemistry Source Type: research

Dual blockade of VEGFR1 and VEGFR2 by a novel peptide abrogates VEGF-driven angiogenesis, tumor growth, and metastasis through PI3K/AKT and MAPK/ERK1/2 pathway
ConclusionThe dual specificity of VGB for VEGFR1 and VEGFR2, through which the PI3K/AKT and MAPK/ERK1/2 signaling pathways can be abrogated and, subsequently, angiogenesis, tumor growth, and metastasis are inhibited.General significance.This study demonstrated that simultaneous blockade of VEGFR1 and VEGFR2 downstream cascades is an effective means for treatment of various angiogenic disorders, especially cancer. (Source: Biochimica et Biophysica Acta (BBA) General Subjects)
Source: Biochimica et Biophysica Acta (BBA) General Subjects - August 21, 2018 Category: Biochemistry Source Type: research

Multimodal highly fluorescent-magnetic nanoplatform to target transferrin receptors in cancer cells
ConclusionsThe prepared BNPs-Tf hold great promise as an effective and specific multimodal, highly fluorescent-magnetic, nanoplatform for fluorescence analyses and T2-weighted images.General significance.This study developed an attractive and versatile multimodal nanoplatform that has potential to be applied in a variety of in vitro and in vivo studies, addressing biological processes, diagnostic, and therapeutics. Moreover, this work opens new possibilities for designing other efficient multimodal nanosystems, considering other biomolecules in their composition able to provide them important functional properties.Graphica...
Source: Biochimica et Biophysica Acta (BBA) General Subjects - August 21, 2018 Category: Biochemistry Source Type: research

Biochemical characterization of protoporphyrinogen dehydrogenase and protoporphyrin ferrochelatase of Vibrio vulnificus and the critical complex formation between these enzymes
ConclusionThe PdgH1-PpfC complex is important for protective channeling of PPn and for efficient catalysis of free PPn. The production of PPn by PgdH1 is regulated by feedback inhibition by heme.General significance: Both proteobacteria and eukaryotes have evolved mechanisms to prevent the harmful accumulation of the heme biosynthesis intermediate PPn. The data presented here suggest two previously unknown mechanisms: the channeling of PPn through the PgdH1-PpfC complex, and the direct inhibition of PgdH1 activity (PgoX activity as well) by heme. (Source: Biochimica et Biophysica Acta (BBA) General Subjects)
Source: Biochimica et Biophysica Acta (BBA) General Subjects - August 21, 2018 Category: Biochemistry Source Type: research

Editorial Board
Publication date: October 2018Source: Biochimica et Biophysica Acta (BBA) - General Subjects, Volume 1862, Issue 10Author(s): (Source: Biochimica et Biophysica Acta (BBA) General Subjects)
Source: Biochimica et Biophysica Acta (BBA) General Subjects - August 15, 2018 Category: Biochemistry Source Type: research