1,010 results match your criteria Biochimica Et Biophysica Acta-general Subjects[Journal]


Composite 5-methylations of cytosines modulate i-motif stability in a sequence-specific manner: Implications for DNA nanotechnology and epigenetic regulation of plant telomeric DNA.

Biochim Biophys Acta Gen Subj 2020 May 31:129651. Epub 2020 May 31.

Central European Institute of Technology, Masaryk University, Brno 625 00, Czechia. Electronic address:

Background: The i-motif is a tetrameric DNA structure based on the formation of hemiprotonated cytosine-cytosine (C.C) base pairs. i-Motifs are widely used in nanotechnology. Read More

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http://dx.doi.org/10.1016/j.bbagen.2020.129651DOI Listing

Inosine 5'-diphosphate, a molecular decoy rescues Nucleoside diphosphate kinase from c-MYC G-Quadruplex unfolding.

Biochim Biophys Acta Gen Subj 2020 May 31:129649. Epub 2020 May 31.

Department of Biophysics, Bose Institute, Centenary Campus, P-1/12, C.I.T. Scheme VIIM, Kankurgachi, Kolkata 700054, India. Electronic address:

Background: The transcription-inhibitory G-Quadruplex(Pu27-GQ) atc-MYCpromoter is challenging to target due to structural heterogeneity. Nucleoside diphosphate kinase (NM23-H2) specifically binds and unfolds Pu27-GQ to increasec-MYC transcription. Here, we used Inosine 5'-diphosphate (IDP) to disrupt NM23-H2-Pu27-GQ interactions and arrest c-MYC transcription without compromising NM23-H2-mediated kinase properties. Read More

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http://dx.doi.org/10.1016/j.bbagen.2020.129649DOI Listing

Imaging extracelluar vesicles by transmission electron microscopy: Coping with technical hurdles and morphological interpretation.

Biochim Biophys Acta Gen Subj 2020 May 30:129648. Epub 2020 May 30.

Department of Veterinary Medicine, University of Perugia, Via S. Costanzo, 4, Perugia, Italy.

Background: Extracellular vesicles (EVs) are cell-derived nanometric particles governing the complex interactions among cells through their bioactive cargo. Interest in EVs is rapidly increasing due to their extensive involvement in physiological and pathological conditions, their potential employment as diagnostic and therapeutic tools and their prospective use as bio-carriers of exogenous molecules. Given their nanometric size, transmission electron microscopy (TEM) provides significant contributions to assess EV presence and purity in a sample and to study morphological features. Read More

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http://dx.doi.org/10.1016/j.bbagen.2020.129648DOI Listing

Mitochondrial research in Asia: A step for the mito-global conference.

Biochim Biophys Acta Gen Subj 2020 May 28:129638. Epub 2020 May 28.

Department of Neurology, Juntendo University Graduate School of Medicine, Japan.

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http://dx.doi.org/10.1016/j.bbagen.2020.129638DOI Listing

The fibrinogen C-terminal domain is seldom C-mannosylated but its C-mannosylation is important for the secretion of microfibril-associated glycoprotein 4.

Biochim Biophys Acta Gen Subj 2020 May 19;1864(9):129637. Epub 2020 May 19.

Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 223-8522, Japan. Electronic address:

Background: C-mannosylation is the one of glycosylations. Microfibril-associated glycoprotein 4 (MFAP4), an important protein for tissue homeostasis and cell adhesion, contains a consensus sequence of C-mannosylation in its fibrinogen C-terminal domain. In this study, we sought to demonstrate that fibrinogen C-terminal domain is a new substrate domain for C-mannosylation. Read More

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http://dx.doi.org/10.1016/j.bbagen.2020.129637DOI Listing

Human proline specific peptidases: A comprehensive analysis.

Biochim Biophys Acta Gen Subj 2020 May 17;1864(9):129636. Epub 2020 May 17.

A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia.

Background: Proline specific peptidases (PSPs) are a unique group of enzymes that specifically cleave bonds formed by a proline residue. The study of PSPs is important due to their role in the maturation and degradation of peptide hormones and neuropeptides. In addition, changes in the activity of PSPs can result in pathological conditions, including various types of cancer. Read More

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http://dx.doi.org/10.1016/j.bbagen.2020.129636DOI Listing

AMPK is essential for IL-10 expression and for maintaining balance between inflammatory and cytoprotective signaling.

Biochim Biophys Acta Gen Subj 2020 Aug 11;1864(8):129631. Epub 2020 May 11.

College of Pharmacy, Yeungnam University, Gyeongsan 38541, Republic of Korea. Electronic address:

Background: AMP-activated protein kinase (AMPK) exerts its anti-inflammatory effects by suppressing redox-sensitive nuclear factor kappa B (NF-κB) and pro-inflammatory cytokines including TNF-α. However, it is unclear whether AMPK regulates anti-inflammatory cytokine expressions in the presence of oxidative stress-induced inflammation. We sought to elucidate the mechanisms whereby AMPK regulates inflammatory cytokine expressions under NADPH oxidase (NOX)-induced oxidative stress. Read More

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http://dx.doi.org/10.1016/j.bbagen.2020.129631DOI Listing

O-linked N-acetylgalactosamine modification is present on the tumor suppressor p53.

Biochim Biophys Acta Gen Subj 2020 Aug 14;1864(8):129635. Epub 2020 May 14.

Key Laboratory of Systems Biomedicine (Ministry of Education) and Collaborative Innovation Center of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China; SCSB (China)-AIST (Japan) Joint Medical Glycomics Laboratory, Shanghai, China. Electronic address:

Background: Mucin-type O-glycosylation (referred to as O-GalNAc glycosylation) is the most abundant O-glycosylation on membrane and secretory proteins. Recently several evidences suggest that nuclear or cytoplasmic proteins might also have O-GalNAc glycosylation. However, what nucleocytoplasmic proteins are O-GalNAc glycosylated and what the biological function of this modification in cells are still poorly understood. Read More

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http://dx.doi.org/10.1016/j.bbagen.2020.129635DOI Listing

Mitochondria as targets for toxicity and metabolism research using zebrafish.

Biochim Biophys Acta Gen Subj 2020 Aug 15;1864(8):129634. Epub 2020 May 15.

Biochemistry Department, Federal University of Pernambuco - UFPE, Recife, PE, Brazil.

Background: The study of mitochondrial functions in zebrafish was initiated before the 1990s and has effectively supported many of the recent scientific advances in the functional studies of mitochondria.

Scope Of Review: This work elaborates various peculiarities and general advances in the study of mitochondria using this animal model.

Major Conclusions: The inclusion of zebrafish models in scientific research was initiated with structural studies of mitochondria. Read More

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http://dx.doi.org/10.1016/j.bbagen.2020.129634DOI Listing

EcDBS1R6: A novel cationic antimicrobial peptide derived from a signal peptide sequence.

Biochim Biophys Acta Gen Subj 2020 May 13;1864(9):129633. Epub 2020 May 13.

S-Inova Biotech, Pós-graduação em Biotecnologia, Universidade Católica Dom Bosco, Campo Grande, MS, Brazil; Centro de Análises Proteômicas e Bioquímicas, Pós-Graduação em Ciências Genômicas e Biotecnologia Universidade Católica de Brasília, Brasília, DF, Brazil; Molecular Pathology Post-graduate Program, University of Brasília, Brasília, Distrito Federal, Brazil. Electronic address:

Background: Bacterial infections represent a major worldwide health problem the antimicrobial peptides (AMPs) have been considered as potential alternative agents for treating these infections. Here we demonstrated the antimicrobial activity of EcDBS1R6, a peptide derived from a signal peptide sequence of Escherichia coli that we previously turned into an AMP by making changes through the Joker algorithm.

Methods: Antimicrobial activity was measured by broth microdilution method. Read More

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http://dx.doi.org/10.1016/j.bbagen.2020.129633DOI Listing

Role of C-mannosylation in the secretion of mindin.

Biochim Biophys Acta Gen Subj 2020 Aug 19;1864(8):129632. Epub 2020 May 19.

Department of Biochemistry, School of Medicine, Wakayama Medical University, Wakayama 641-0012, Japan. Electronic address:

Background: Mindin (spondin2), a secretory protein related to neural development and immunity, is a member of thrombospondin type I repeat (TSR) superfamily proteins, and has a unique glycosylation of C-mannosylation in its structure. However, it remains unclear whether C-mannosylation plays a functional role in the biosynthesis of mindin in cells.

Methods: Protein C-mannosylation was analyzed by mass spectrometry. Read More

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http://dx.doi.org/10.1016/j.bbagen.2020.129632DOI Listing

New insights into serum/extracellular thioredoxin in regulating hepatic insulin receptor activation.

Biochim Biophys Acta Gen Subj 2020 Aug 4;1864(8):129630. Epub 2020 May 4.

Medical School, University of Chinese Academy of Sciences, the Campus of Yanqi, Huai Rou, Beijing 101407, China. Electronic address:

Background: Serum thioredoxin of type-2 diabetic patients is significantly higher than that of healthy people. Pathophysiological significance is unclear.

Methods: Effects of serum/extracellular thioredoxin on phosphorylation (activation) of hepatic insulin receptor (IR) were investigated by using methods in biochemistry, cell/molecular biology and mass spectrometry. Read More

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http://dx.doi.org/10.1016/j.bbagen.2020.129630DOI Listing

Matrix vesicle biomimetics harboring Annexin A5 and alkaline phosphatase bind to the native collagen matrix produced by mineralizing vascular smooth muscle cells.

Biochim Biophys Acta Gen Subj 2020 Aug 29;1864(8):129629. Epub 2020 Apr 29.

Department of Chemistry, FFCLRP-USP, University of São Paulo, Ribeirão Preto, SP, Brazil. Electronic address:

Backgound: Vascular smooth muscle cells (VSMCs) transdifferentiated ectopically trigger vascular calcifications, contributing to clinical cardiovascular disease in the aging population. AnxA5 and TNAP play a crucial role in (patho)physiological mineralization.

Methods: We performed affinity studies between DPPC and 9:1 DPPC:DPPS-proteoliposomes carrying AnxA5 and/or TNAP and different types of collagen matrix: type I, II, I + III and native collagenous extracellular matrix (ECM) produced from VSMCs with or without differentiation, to simulate ectopic calcification conditions. Read More

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http://dx.doi.org/10.1016/j.bbagen.2020.129629DOI Listing

The multiple activities of BAG3 protein: Mechanisms.

Biochim Biophys Acta Gen Subj 2020 Aug 28;1864(8):129628. Epub 2020 Apr 28.

Department of Medicine, Surgery and Dentistry Schola Medica Salernitana, University of Salerno, Baronissi, SA 84081, Italy. Electronic address:

Background: BAG3 was identified as a co-chaperone of the heat shock protein (Hsp) 70, which helps, through the binding to the ATPase domain, the ADP release from the chaperone and the nucleotide cycling. By interacting with Hsp70, BAG3 modulates the activities of this chaperone, including the delivery of client proteins to proteasome. BAG3 can also carry out Hsp70- independent functions, through its interactions with other proteins involved in apoptosis, cytoskeleton dynamics and other pathways. Read More

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http://dx.doi.org/10.1016/j.bbagen.2020.129628DOI Listing

Immune modulations and survival strategies of evolved hypervirulent Salmonella Typhimurium strains.

Biochim Biophys Acta Gen Subj 2020 Aug 28;1864(8):129627. Epub 2020 Apr 28.

Laboratory of Infection Immunology, Department of Life Science, National Institute of Technology, Rourkela, Odisha 769008, India. Electronic address:

Background: Evolving multidrug-resistance and hypervirulence in Salmonella is due to multiple host-pathogen, and non-host environmental interactions. Previously we had studied Salmonella adaptation upon repeated exposure in different in-vitro and in-vivo environmental conditions. This study deals with the mechanistic basis of hypervirulence of the passaged hypervirulent Salmonella strains reported previously. Read More

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http://dx.doi.org/10.1016/j.bbagen.2020.129627DOI Listing
August 2020
4.381 Impact Factor

NDRG1 suppresses basal and hypoxia-induced autophagy at both the initiation and degradation stages and sensitizes pancreatic cancer cells to lysosomal membrane permeabilization.

Biochim Biophys Acta Gen Subj 2020 Aug 23;1864(8):129625. Epub 2020 Apr 23.

Molecular Pharmacology and Pathology Program, Department of Pathology and Bosch Institute, Medical Foundation Building (K25), University of Sydney, Sydney, New South Wales 2006, Australia; Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan; Centre for Cancer Cell Biology, Griffith Institute for Drug Discovery, Griffith University, Nathan, Brisbane, Queensland, Australia. Electronic address:

Background: N-myc downstream regulated gene 1 (NDRG1) is an established stress-response protein. This study investigated the effects of NDRG1 on autophagic degradation and how this can be therapeutically exploited.

Methods: Cell culture, western analysis, confocal microscopy, acridine orange staining, cholesterol determination, cellular proliferation assessment and combination index (CI) estimation. Read More

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http://dx.doi.org/10.1016/j.bbagen.2020.129625DOI Listing

TAT-tagging of VIP exerts positive allosteric modulation of the PAC1 receptor and enhances VIP neuroprotective effect in the MPTP mouse model of Parkinson's disease.

Biochim Biophys Acta Gen Subj 2020 Aug 23;1864(8):129626. Epub 2020 Apr 23.

Normandie Univ, UNIROUEN, Inserm, Laboratory of Neuronal and Neuroendocrine Communication and Differentiation, Neuropeptides, Neuronal Death, Cell plasticity Team, Rouen, France.

Background: The cationic Arginine-rich peptide (CARP) TAT had been tagged at the C-terminal end of the vasoactive intestinal peptide (VIP) to construct VIP-TAT in order to improve traversing ability. Interestingly, it was found that TAT may bind the positive allosteric modulation (PAM) site of the N-terminal extracellular domain of neuropeptide receptor PAC1 (PAC1-EC1), imitating the C-terminus part of pituitary adenylate cyclase-activating polypeptide (PACAP) PACAP(28-38) fragment.

Methods: To test this hypothesis, we addressed the neuroprotective effects of VIP, VIP-TAT and PACAP38 in Parkinson's Disease (PD) cellular and mouse models. Read More

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http://dx.doi.org/10.1016/j.bbagen.2020.129626DOI Listing

Proton transfer in the D-channel of cytochrome c oxidase modeled by a transition network approach.

Biochim Biophys Acta Gen Subj 2020 Aug 17;1864(8):129614. Epub 2020 Apr 17.

Department of Physics, Freie Universität Berlin, Arnimallee 14, 14159 Berlin, Germany. Electronic address:

Background: Determination of proton uptake pathways in Cytochrome c Oxidase is difficult due to the complexity of the system. The transition networks approach allows sampling of proton transfer pathways without predefined reaction coordinate.

Methods: Computation of the proton transfer pathways in a model of the D-channel of cytochrome c oxidase has been performed by a transition network approach that combines discrete, optimisation based and molecular dynamics based sampling. Read More

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http://dx.doi.org/10.1016/j.bbagen.2020.129614DOI Listing

Profiling calcium-dependent interactions between Sorcin and intrinsically disordered regions of human proteome.

Biochim Biophys Acta Gen Subj 2020 Aug 17;1864(8):129618. Epub 2020 Apr 17.

Department of Chemistry - BMC, Uppsala University, Husargatan 3, 751 23 Uppsala, Sweden.

Background: Sorcin is a calcium sensor that exerts many calcium-related functions in the cells, e.g. it regulates calcium concentration in the cytoplasm, endoplasmic reticulum (ER) and mitochondria, by interacting with calcium pumps, exchangers and channels. Read More

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http://dx.doi.org/10.1016/j.bbagen.2020.129618DOI Listing

A ring-shaped protein clusters gold nanoparticles acting as molecular scaffold for plasmonic surfaces.

Biochim Biophys Acta Gen Subj 2020 Aug 15;1864(8):129617. Epub 2020 Apr 15.

Department of Life, Health and Environmental Sciences, University of L'Aquila, Piazzale Salvatore Tommasi 1, 67100 Coppito, L'Aquila, Italy. Electronic address:

Background: Proteins are efficient supramolecular scaffolds to drive self-assembly of nanomaterials into regular colloidal structures suitable for several purposes, including cell imaging and drug delivery. Proteins, in particular, can bind to gold nanoparticles (AuNPs) through van der Waals and electrostatic forces as well as coordination and hydrogen bonds leading their assembly into responsive nanostructures.

Methods: Bioconjugation of alkyne Raman tag-labeled 20 nm AuNPs with the ring-shaped protein Peroxiredoxin (Prx), characterized by a symmetric homo-oligomeric circular arrangement, has been investigated by absorption spectroscopy, transmission and scanning electron microscopy. Read More

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http://dx.doi.org/10.1016/j.bbagen.2020.129617DOI Listing

Retrospective ensemble docking of allosteric modulators in an adenosine G-protein-coupled receptor.

Biochim Biophys Acta Gen Subj 2020 Aug 13;1864(8):129615. Epub 2020 Apr 13.

Center for Computational Biology and Department of Molecular Biosciences, University of Kansas, Lawrence, KS 66047, USA. Electronic address:

Background: Ensemble docking has proven useful in drug discovery and development. It increases the hit rate by incorporating receptor flexibility into molecular docking as demonstrated on important drug targets including G-protein-coupled receptors (GPCRs). Adenosine A receptor (AAR) is a key GPCR that has been targeted for treating cardiac ischemia-reperfusion injuries, neuropathic pain and renal diseases. Read More

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http://dx.doi.org/10.1016/j.bbagen.2020.129615DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7261249PMC

Protein mechanics probed using simple molecular models.

Biochim Biophys Acta Gen Subj 2020 Aug 13;1864(8):129613. Epub 2020 Apr 13.

Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, United Kingdom. Electronic address:

Background: Single-molecule experimental techniques such as optical tweezers or atomic force microscopy are a direct probe of the mechanical unfolding/folding of individual proteins. They are also a means to investigate free energy landscapes. Protein force spectroscopy alone provides limited information; theoretical models relate measurements to thermodynamic and kinetic properties of the protein, but do not reveal atomic level information. Read More

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http://dx.doi.org/10.1016/j.bbagen.2020.129613DOI Listing

Robosample: A rigid-body molecular simulation program based on robot mechanics.

Biochim Biophys Acta Gen Subj 2020 Aug 13;1864(8):129616. Epub 2020 Apr 13.

Department of Bioinformatics and Structural Biochemistry, Institute of Biochemistry of the Romanian Academy, Splaiul Independentei 296, Bucharest 060031, Romania. Electronic address:

Background: Compared with all-atom molecular dynamics (MD), constrained MD methods allow for larger time steps, potentially reducing computational cost. For this reason, there has been continued interest in improving constrained MD algorithms to increase configuration space sampling in molecular simulations.

Methods: Here, we introduce Robosample, a software package that implements high-performance constrained dynamics algorithms, originally developed for robotics, and applies them to simulations of biomolecular systems. Read More

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http://dx.doi.org/10.1016/j.bbagen.2020.129616DOI Listing

Metabolic characterization of a paused-like pluripotent state.

Biochim Biophys Acta Gen Subj 2020 Aug 6;1864(8):129612. Epub 2020 Apr 6.

CNC-Center for Neuroscience and Cell Biology, CIBB, Azinhaga de Santa Comba, Polo 3, University of Coimbra, Coimbra, Portugal; University of Coimbra, Department of Life Sciences, Calçada Martim de Freitas, 3000-456 Coimbra, Portugal. Electronic address:

Embryonic diapause is a conserved reproductive strategy in which development arrests at the blastocyst phase. Recently mammalian target of rapamycin (mTOR) inhibition was shown to induce diapause on mouse blastocysts and a paused-like state on mouse embryonic stem cells (mESCs). In this work, we aimed to further characterize this new paused-pluripotent state, focusing on its glycolytic and oxidative metabolic function. Read More

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http://dx.doi.org/10.1016/j.bbagen.2020.129612DOI Listing

Hybrid giant lipid vesicles incorporating a PMMA-based copolymer.

Biochim Biophys Acta Gen Subj 2020 Apr 7:129611. Epub 2020 Apr 7.

Department of Earth, Environmental and Physical Sciences - DEEP Sciences - Pian dei Mantellini 44, 53100 Siena, Italy.

Background: In recent years, there has been a growing interest in the formation of copolymer-lipid hybrid self-assemblies, which allow combining and improving the main features of pure lipid-based and copolymer-based systems known for their potential applications in the biomedical field. As the most common method used to obtain giant vesicles is electroformation, most systems so far used low T polymers for their flexibility at room temperature.

Methods: Copolymers used in the hybrid vesicles have been synthesized by a modified version of the ATRP, namely the Activators ReGenerated by Electron Transfer ATRP and characterized by NMR and DSC. Read More

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http://dx.doi.org/10.1016/j.bbagen.2020.129611DOI Listing

Regulatory expression of bone morphogenetic protein 6 by 2,2'-dipyridyl.

Biochim Biophys Acta Gen Subj 2020 Aug 3;1864(8):129610. Epub 2020 Apr 3.

Division of Applied Biosciences, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan. Electronic address:

Background: Expression of hepcidin, a hormone produced by hepatocytes which negatively regulates the circulating iron levels, is known to be positively regulated by BMP6, a member of transforming growth factor (TGF)-β family. Previous studies have shown that iron status is sensed by sinusoidal endothelial cells of hepatic lamina, leading to the modulation of BMP6 expression.

Methods: ISOS-1, HUVEC, F-2, and SK-HEP1 endothelial cells were treated with either iron or 2,2'-dipyridyl (2DP), a cell-permeable iron-chelator, and expression level of Bmp6 was examined. Read More

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http://dx.doi.org/10.1016/j.bbagen.2020.129610DOI Listing

Release of extracellular vesicle miR-494-3p by ARPE-19 cells with impaired mitochondria.

Biochim Biophys Acta Gen Subj 2020 Mar 30:129598. Epub 2020 Mar 30.

Center for Nanomedicine, Wilmer Eye Institute, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States of America. Electronic address:

Background: Mitochondrial function in retinal pigmented epithelial (RPE) cells and extracellular vesicle (EV) formation/release are related through the lysosomal and exocytotic pathways that process and eliminate intracellular material, including mitochondrial fragments. We propose that RPE cells with impaired mitochondria will release EVs containing mitochondrial miRNAs that reflect the diminished capacity of mitochondria within these cells.

Methods: We screened ARPE-19 cells for miRNAs that localize to the mitochondria, exhibit biological activity, and are present in EVs released by both untreated cells and cells treated with rotenone to induce mitochondrial injury. Read More

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http://dx.doi.org/10.1016/j.bbagen.2020.129598DOI Listing

Modeling of pathogenic variants of mitochondrial DNA polymerase: insight into the replication defects and implication for human disease.

Biochim Biophys Acta Gen Subj 2020 Jul 29;1864(7):129608. Epub 2020 Mar 29.

Laboratorio Nacional de Genómica para la Biodiversidad, Centro de Investigación y de Estudios Avanzados del IPN, Apartado Postal 629, CP 36821 Irapuato, Guanajuato, Mexico. Electronic address:

Background: Mutations in human gene encoding the mitochondrial DNA polymerase γ (HsPolγ) are associated with a broad range of mitochondrial diseases. Here we studied the impact on DNA replication by disease variants clustered around residue HsPolγ-K1191, a residue that in several family-A DNA polymerases interacts with the 3' end of the primer.

Methods: Specifically, we examined the effect of HsPolγ carrying pathogenic variants in residues D1184, I1185, C1188, K1191, D1196, and a stop codon at residue T1199, using as a model the yeast mitochondrial DNA polymerase protein, Mip1p. Read More

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http://dx.doi.org/10.1016/j.bbagen.2020.129608DOI Listing

Human importin α3 and its N-terminal truncated form, without the importin-β-binding domain, are oligomeric species with a low conformational stability in solution.

Biochim Biophys Acta Gen Subj 2020 Jul 29;1864(7):129609. Epub 2020 Mar 29.

IDIBE, Universidad Miguel Hernández, 03202 Elche, Alicante, Spain; Instituto de Biocomputación y Física de Sistemas Complejos, Joint Units IQFR-CSIC-BIFI, and GBsC-CSIC-BIFI, Universidad de Zaragoza, 50009 Zaragoza, Spain. Electronic address:

Background: Eukaryotic cells have a continuous transit of macromolecules between the cytoplasm and the nucleus. Several carrier proteins are involved in this transport. One of them is importin α, which must form a complex with importin β to accomplish its function, by domain-swapping its 60-residue-long N terminus. Read More

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http://dx.doi.org/10.1016/j.bbagen.2020.129609DOI Listing

High-affinity binding and catalytic activity of His/Tyr-based sequences: Extending heme-regulatory motifs beyond CP.

Biochim Biophys Acta Gen Subj 2020 Jul 29;1864(7):129603. Epub 2020 Mar 29.

Pharmaceutical Biochemistry and Bioanalytics, Pharmaceutical Institute, University of Bonn, 53121 Bonn, Germany. Electronic address:

Background & Motivation: Peptides and proteins can interact with heme through His, Tyr, or Cys in heme-regulatory motifs (HRMs). The Cys-Pro dipeptide is a well investigated HRM, but for His and Tyr such a distinct motif is currently unknown. In addition, many heme-peptide complexes, such as heme-amyloid β, can display a peroxidase-like activity, albeit there is little understanding of how the local primary and secondary coordination environment influences catalytic activity. Read More

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http://dx.doi.org/10.1016/j.bbagen.2020.129603DOI Listing

The antimicrobial peptide Temporin L impairs E. coli cell division by interacting with FtsZ and the divisome complex.

Biochim Biophys Acta Gen Subj 2020 Jul 27;1864(7):129606. Epub 2020 Mar 27.

Department of Pharmaceutical Sciences, University of Milan, Via Venezian 21, 20133 Milan, Italy. Electronic address:

Background: The comprehension of the mechanism of action of antimicrobial peptides is fundamental for the design of new antibiotics. Studies performed looking at the interaction of peptides with bacterial cells offer a faithful picture of what really happens in nature.

Methods: In this work we focused on the interaction of the peptide Temporin L with E. Read More

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http://dx.doi.org/10.1016/j.bbagen.2020.129606DOI Listing

Glycine substitution in SH3-SH2 connector of Hck tyrosine kinase causes population shift from assembled to disassembled state.

Biochim Biophys Acta Gen Subj 2020 Jul 26;1864(7):129604. Epub 2020 Mar 26.

Department of Biochemistry and Molecular Biology, University of Chicago, 929 East 57th Street, Chicago, IL 60637, United States of America; Biosciences Division, Argonne National Laboratory, Argonne, IL 60439, United States of America. Electronic address:

A combination of small angle X-ray scattering (SAXS) and molecular dynamics (MD) simulations based on a coarse grained model is used to examine the effect of glycine substitutions in the short connector between the SH3 and SH2 domains of Hck, a member of the Src-family kinases. It has been shown previously that the activity of cSrc kinase is upregulated by substitution of 3 residues by glycine in the SH3-SH2 connector. Here, analysis of SAXS data indicates that the population of Hck in the disassembled state increases from 25% in the wild type kinase to 76% in the glycine mutant. Read More

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http://dx.doi.org/10.1016/j.bbagen.2020.129604DOI Listing

A multi-approach analysis highlights the relevance of RPA-1 as a telomere end-binding protein (TEBP) in Leishmania amazonensis.

Biochim Biophys Acta Gen Subj 2020 Jul 25;1864(7):129607. Epub 2020 Mar 25.

Department of Chemical and Biological Sciences, São Paulo State University (UNESP) - Botucatu, SP, Brazil. Electronic address:

Background: Telomeres are chromosome end structures important in the maintenance of genome homeostasis. They are replenished by the action of telomerase and associated proteins, such as the OB (oligonucleotide/oligosaccharide-binding)-fold containing telomere-end binding proteins (TEBP) which plays an essential role in telomere maintenance and protection. The nature of TEBPs is well known in higher and some primitive eukaryotes, but it remains undetermined in trypanosomatids. Read More

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http://dx.doi.org/10.1016/j.bbagen.2020.129607DOI Listing

Conformational gating in ammonia lyases.

Biochim Biophys Acta Gen Subj 2020 Jul 25;1864(7):129605. Epub 2020 Mar 25.

Computational Biology Laboratory, Danish Cancer Society Research Center, Copenhagen, Denmark; Translational Disease Systems Biology, Faculty of Health and Medical Sciences, Novo Nordisk Foundation Center for Protein Research University of Copenhagen, Copenhagen, Denmark. Electronic address:

Background: Ammonia lyases are enzymes of industrial and biomedical interest. Knowledge of structure-dynamics-function relationship in ammonia lyases is instrumental for exploiting the potential of these enzymes in industrial or biomedical applications.

Methods: We investigated the conformational changes in the proximity of the catalytic pocket of a 3-methylaspartate ammonia lyase (MAL) as a model system. Read More

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http://dx.doi.org/10.1016/j.bbagen.2020.129605DOI Listing

HIF1α/PLD2 axis linked to glycolysis induces T-cell immunity in oral lichen planus.

Biochim Biophys Acta Gen Subj 2020 Jul 20;1864(7):129602. Epub 2020 Mar 20.

The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, PR China; Department of Oral Medicine, School and Hospital of Stomatology, Wuhan University, PR China. Electronic address:

Background: Oral lichen planus (OLP) is a common T-cell-mediated immunological disease. Hypoxia-inducible factor 1 alpha (HIF1α) plays an integral role in the glycolytic metabolism that facilitates immune functions from boosting cellular proliferative capacity to driving T-cell differentiation. In general, phospholipase D2 (PLD2) is required for HIF1α regulation. Read More

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http://dx.doi.org/10.1016/j.bbagen.2020.129602DOI Listing

A novel, cupin-type phosphoglucose isomerase in Escherichia coli.

Biochim Biophys Acta Gen Subj 2020 Jul 13;1864(7):129601. Epub 2020 Mar 13.

Belozersky Institute of Physico-Chemical Biology and Department of Chemistry, Lomonosov Moscow State University, Moscow, Russia. Electronic address:

Background: Escherichia coli cells contain a homolog of presumed 5-keto-4-deoxyuronate isomerase (KduI) from pectin-degrading soil bacteria, but the catalytic activity of the E. coli protein (o-KduI) was never demonstrated.

Methods: The known three-dimensional structure of E. Read More

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Stacking geometry between two sheared Watson-Crick basepairs: Computational chemistry and bioinformatics based prediction.

Biochim Biophys Acta Gen Subj 2020 Jul 14;1864(7):129600. Epub 2020 Mar 14.

Computational Science Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata 700064, India; Homi Bhaba National Institute, Anushaktinagar, Mumbai 400094, India. Electronic address:

Background: Molecular modeling of RNA double helices is possible using most probable values of basepair parameters obtained from crystal structure database. The A:A w:wC non-canonical basepair, involving Watson-Crick edges of two Adenines in cis orientation, appears quite frequently in database. Bimodal distribution of its Shear, due to two different H-bonding schemes, introduces the confusion in assigning most the probable value. Read More

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http://dx.doi.org/10.1016/j.bbagen.2020.129600DOI Listing

The cytosolic isoform of glutaredoxin 2 promotes cell migration and invasion.

Biochim Biophys Acta Gen Subj 2020 Jul 12;1864(7):129599. Epub 2020 Mar 12.

Institute for Medical Biochemistry and Molecular Biology, University Medicine, University Greifswald, Germany. Electronic address:

Backround: Cytosolic glutaredoxin 2 (Grx2c) controls axonal outgrowth and is specifically induced in many cancer cell lines. We thus hypothesized that Grx2c promotes cell motility and invasiveness.

Methods: We characterized the impact of Grx2c expression in cell culture models. Read More

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Transgenic models for investigating the nervous system: Currently available neurofluorescent reporters and potential neuronal markers.

Biochim Biophys Acta Gen Subj 2020 Jul 12;1864(7):129595. Epub 2020 Mar 12.

Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, College of Medicine, University of Illinois at Chicago, Chicago, IL, United States of America. Electronic address:

Recombinant DNA technologies have enabled the development of transgenic animal models for use in studying a myriad of diseases and biological states. By placing fluorescent reporters under the direct regulation of the promoter region of specific marker proteins, these models can localize and characterize very specific cell types. One important application of transgenic species is the study of the cytoarchitecture of the nervous system. Read More

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http://dx.doi.org/10.1016/j.bbagen.2020.129595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7196036PMC

A single P115Q mutation modulates specificity in the Corynebacterium pseudotuberculosis arginine repressor.

Biochim Biophys Acta Gen Subj 2020 Jul 7;1864(7):129597. Epub 2020 Mar 7.

Multiuser Center for Biomolecular Innovation, IBILCE/UNESP, São José do Rio Preto, SP, Brazil; Department of Physics, IBILCE/UNESP, São José do Rio Preto, SP, Brazil.

The arginine repressor (ArgR) regulates the expression of genes involved in arginine biosynthesis. Upon attaining a threshold concentration of arginine in the cytoplasm, the trimeric C-terminal domain of ArgR binds three arginines in a shallow surface cleft and subsequently hexamerizes forming a dimer of trimers containing six Arg co-repressor molecules which are buried at the subunit interfaces. The N-terminal domains of this complex bind to the DNA promoter thereby interrupting the transcription of the genes related to Arg biosynthesis. Read More

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Involvement of the α-helical and Src homology 3 domains in the molecular assembly and enzymatic activity of human α1,6-fucosyltransferase, FUT8.

Biochim Biophys Acta Gen Subj 2020 Jul 5;1864(7):129596. Epub 2020 Mar 5.

Division of Molecular Cell Biology, Department of Biomolecular Sciences, Saga University Faculty of Medicine, 5-1-1 Nabeshima, Saga 849-8501, Japan.

Background: Previous structural analyses showed that human α1,6-fucosyltransferase, FUT8 contains a catalytic domain along with two additional domains, N-terminal α-helical domain and C-terminal Src homology 3 domain, but these domains are unique to FUT8 among glycosyltransferases. The role that these domains play in formation of the active form of FUT8 has not been investigated. This study reports on attempts to determine the involvement of these domains in the functions of FUT8. Read More

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QM/MM computations reveal details of the acetyl-CoA synthase catalytic center.

Biochim Biophys Acta Gen Subj 2020 Jul 2;1864(7):129579. Epub 2020 Mar 2.

TU Berlin, 135 Strasse-des-17. Juni, 10623 Berlin, Germany.

The "open" (A) and "closed" (A) A-clusters of the acteyl-CoA synthase (ACS) enzyme from Moorella thermoacetica have been studied using a combined quantum mechanical (QM)/molecular mechanical (MM) approach. Geometry optimizations of the oxidized, one- and two-electron reduced A state have been carried out for the fully solvated ACS enzyme, and the CO ligand has been modeled in the reduced models. Using a combination of both α and α protein scaffolds and the positions of metal atoms in these structures, we have been able to piece together critical parts of the catalytic cycle of ACS. Read More

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Modulation of tau protein aggregation using 'Trojan' sequences.

Biochim Biophys Acta Gen Subj 2020 Jul 27;1864(7):129569. Epub 2020 Feb 27.

Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati 781039, India. Electronic address:

Background: The abnormal assembly of tau into neurofibrillary tangles has been associated with over 30 debilitating disorders known as tauopathies. Tauopathies affect millions of people worldwide, yet no clinically approved solution for tau aggregation is currently available.

Methods: We employed a structure-based design approach to make a series of short peptide-based perturbants (Trojans), that can interact with the core hydrophobic fragment of tau protein. Read More

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BamA is required for autotransporter secretion.

Biochim Biophys Acta Gen Subj 2020 Jul 27;1864(7):129581. Epub 2020 Feb 27.

School of Physics, Georgia Institute of Technology, Atlanta, GA 30313, United States of America. Electronic address:

Background: In Gram-negative bacteria, type Va and Vc autotransporters are proteins that contain both a secreted virulence factor (the "passenger" domain) and a β-barrel that aids its export. While it is known that the folding and insertion of the β-barrel domain utilize the β-barrel assembly machinery (BAM) complex, how the passenger domain is secreted and folded across the membrane remains to be determined. The hairpin model states that passenger domain secretion occurs independently through the fully-formed and membrane-inserted β-barrel domain via a hairpin folding intermediate. Read More

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7196024PMC

N-glycosylation state of TRPM8 protein revealed by terahertz spectroscopy and molecular modelling.

Biochim Biophys Acta Gen Subj 2020 Jul 25;1864(7):129580. Epub 2020 Feb 25.

Department DAFAB, Faculty of Biology, University of Bucharest, Splaiul Independenței 91-95, Bucharest, Romania. Electronic address:

TRPM8 member of the TRP superfamily of membrane proteins participates to various cellular processes ranging from Ca uptake and cold sensation to cellular proliferation and migration. TRPM8 is a large tetrameric protein with more than 70% of its residues located in the cytoplasm. TRPM8 is N-glycosylated, with a single site per subunit. Read More

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Aggregation of Lipid A Variants: A Hybrid Particle-Field Model.

Biochim Biophys Acta Gen Subj 2020 Feb 24:129570. Epub 2020 Feb 24.

Department of Organic Material Science, Yamagata University, Yonezawa 992-8510, Japan.

Lipid A is one of the three components of bacterial lipopolysaccharides constituting the outer membrane of Gram-negative bacteria, and is recognized to have an important biological role in the inflammatory response of mammalians. Its biological activity is modulated by the number of acyl-chains that are present in the lipid and by the dielectric medium, i.e. Read More

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February 2020

Cadmium elicits alterations in mitochondrial morphology and functionality in C3H10T1/2Cl8 mouse embryonic fibroblasts.

Biochim Biophys Acta Gen Subj 2020 Aug 20;1864(8):129568. Epub 2020 Feb 20.

Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza, 2, 20126 Milan, Italy; Integrated Models for Prevention and Protection in Environmental and Occupational Health, (MISTRAL), Interuniversity Research Center, Italy.

Background: Cadmium is a widespread carcinogen. We previously showed that the administration of low CdCl doses for 24 h to healthy C3H10T1/2Cl8 mouse embryonic fibroblast cell line at the beginning of Cell Transformation Assay (CTA), up regulates genes involved in metal scavenging and antioxidant defense, like metallothioneines, glutathione S-transferases and heat shock proteins. Still, although most cells thrive normally in the following weeks, malignancy is triggered by CdCl and leads to the appearance of foci of transformed cells at the end of the CTA. Read More

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Liver-derived extracellular vesicles: A cell by cell overview to isolation and characterization practices.

Biochim Biophys Acta Gen Subj 2020 Feb 19:129559. Epub 2020 Feb 19.

Department of Chemistry and Biochemistry, University of Bern, Switzerland. Electronic address:

Background: Extracellular vesicles (EVs) are a diverse group of membrane-bound nanovesicles potentially released by every cell. With the liver's unique ensemble of cells and its fundamental physiological tasks, elucidating the role of EV-mediated hepatic cellular crosstalk and their role in different pathologies has been gaining the attention of many scientists.

Scope Of Review: The present review shifts the perspective into practice: we aim to critically discuss the methods used to purify and to biochemically analyse EVs from specific liver resident cells, including hepatocytes, hepatic stellate cells, cholangiocytes, liver sinusoidal endothelial cells, Kupffer cells, liver stem cells. Read More

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February 2020

A dual PI3 kinase/mTOR inhibitor BEZ235 reverses doxorubicin resistance in ABCB1 overexpressing ovarian and pancreatic cancer cell lines.

Biochim Biophys Acta Gen Subj 2020 Jun 14;1864(6):129556. Epub 2020 Feb 14.

VCU Pauley Heart Center, Division of Cardiology, Virginia Commonwealth University, Richmond, VA 23298, United States. Electronic address:

Background: Multi-drug resistance (MDR) develops because cancer cells evade toxicity of several structurally unrelated drugs. Besides other mechanisms, MDR is linked to the overexpression of ATP Binding Cassette (ABC), transporters, among which ABCB1 is the best characterized one. Since overactivation of PI3K/Akt/mTOR plays a pivotal role in the growth of human cancers, we hypothesized whether dual PI3K and mTOR inhibitor, BEZ235 (BEZ, dactolisib) reverses resistance to doxorubicin (DOX). Read More

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http://dx.doi.org/10.1016/j.bbagen.2020.129556DOI Listing