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https://www.readbyqxmd.com/read/28340332/super-elongation-complex-promotes-early-hiv-transcription-and-its-function-is-modulated-by-p-tefb
#1
Alona Kuzmina, Simona Krasnopolsky, Ran Taube
Early work on the control of transcription of the human immunodeficiency virus (HIV) laid the foundation for our current knowledge of how RNA Polymerase II is released from promoter-proximal pausing sites and transcription elongation is enhanced. The viral Tat activator recruits Positive Transcription Elongation Factor b (P-TEFb) and Super Elongation Complex (SEC) that jointly drive transcription elongation. While substantial progress in understanding the role of SEC in HIV gene transcription elongation has been obtained, defining of the mechanisms that govern SEC functions is still limited, and the role of SEC in controlling HIV transcription in the absence of Tat is less clear...
February 17, 2017: Transcription
https://www.readbyqxmd.com/read/28335523/-2-2-photodimerization-of-naphthylvinylpyridines-through-cation-%C3%AF-interactions-in-acidic-solution
#2
Shinji Yamada, Yuka Nojiri
Irradiation of (E)-4-(2-(2-naphthyl)vinyl)pyridine (1a) and (E)-4-(2-(1-naphthyl)vinyl)pyridine (1b) with a 250 W high-pressure mercury lamp in acidic solution afforded synHT dimers in high stereoselectivities. Similar results were obtained by visible light irradiation. On the other hand, when the reactions were carried out under neutral conditions, the stereoselectivities were very low, and the yields were decreased by visible light irradiation. Comparison of the UV-vis spectra between the acidic and the neutral conditions elucidated that the red shift was observed in acidic solutions...
March 20, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28335037/lrsam1-mediated-ubiquitylation-is-disrupted-in-axonal-charcot-marie-tooth-disease-2p
#3
Johanna E Hakonen, Vincenzo Sorrentino, Rossella Avagliano Trezza, Marit B de Wissel, Marlene van den Berg, Boris Bleijlevens, Fred van Ruissen, Ben Distel, Frank Baas, Noam Zelcer, Marian A J Weterman
Charcot-Marie-Tooth (CMT) disease type 2 is a genetically heterogeneous group of inherited neuropathies characterized by motor and sensory deficits as a result of peripheral axonal degeneration. We recently reported a frameshift mutation in the RING domain of LRSAM1 (c.2121_2122dup, p.Leu708Argfs) that encodes an E3 ubiquitin ligase, as the cause of axonal type CMT (CMT2P). However, the frequency of LRSAM1 mutations in CMT2 and the functional basis for their association with disease remains unknown. In this study we evaluated LRSAM1 mutations in two large Dutch cohorts...
March 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28335002/handcuffing-reversal-is-facilitated-by-proteases-and-replication-initiator-monomers
#4
Katarzyna Bury, Katarzyna Wegrzyn, Igor Konieczny
Specific nucleoprotein complexes are formed strictly to prevent over-initiation of DNA replication. An example of those is the so-called handcuff complex, in which two plasmid molecules are coupled together with plasmid-encoded replication initiation protein (Rep). In this work, we elucidate the mechanism of the handcuff complex disruption. In vitro tests, including dissociation progress analysis, demonstrate that the dimeric variants of plasmid RK2 replication initiation protein TrfA are involved in assembling the plasmid handcuff complex which, as we found, reveals high stability...
March 9, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334941/rna-protein-interactions-govern-antiviral-specificity-and-encapsidation-of-broad-spectrum-anti-hiv-reverse-transcriptase-aptamers
#5
Margaret J Lange, Phuong D M Nguyen, Mackenzie K Callaway, Marc C Johnson, Donald H Burke
RNA aptamers that bind HIV-1 reverse transcriptase (RT) inhibit HIV-1 replication, but little is known about potential aptamer-specific viral resistance. During replication, RT interacts with diverse nucleic acids. Thus, the genetic threshold for eliciting resistance may be high for aptamers that make numerous contacts with RT. To evaluate the impact of RT-aptamer binding specificity on replication, we engineered proviral plasmids encoding diverse RTs within the backbone of HIV-1 strain NL4-3. Viruses inhibited by pseudoknot aptamers were rendered insensitive by a naturally occurring R277K variant, providing the first demonstration of aptamer-specific resistance in cell culture...
March 6, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334932/ribosome-dependent-vibrio-cholerae-mrnase-higb2-is-regulated-by-a-%C3%AE-strand-sliding-mechanism
#6
San Hadži, Abel Garcia-Pino, Sarah Haesaerts, Dukas Jurenas, Kenn Gerdes, Jurij Lah, Remy Loris
Toxin-antitoxin (TA) modules are small operons involved in bacterial stress response and persistence. higBA operons form a family of TA modules with an inverted gene organization and a toxin belonging to the RelE/ParE superfamily. Here, we present the crystal structures of chromosomally encoded Vibrio cholerae antitoxin (VcHigA2), toxin (VcHigB2) and their complex, which show significant differences in structure and mechanisms of function compared to the higBA module from plasmid Rts1, the defining member of the family...
February 28, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334906/conformational-polymorphism-or-structural-invariance-in-dna-photoinduced-lesions-implications-for-repair-rates
#7
François Dehez, Hugo Gattuso, Emmanuelle Bignon, Christophe Morell, Elise Dumont, Antonio Monari
DNA photolesions constitute a particularly deleterious class of molecular defects responsible for the insurgence of a vast majority of skin malignant tumors. Dimerization of two adjacent thymines or cytosines mostly gives rise to cyclobutane pyrimidine dimers (CPD) and pyrimidine(6-4)pyrimidone 64-PP as the most common defects. We perform all-atom classical simulations, up to 2 μs, of CPD and 64-PP embedded in a 16-bp duplex, which reveal the constrasted behavior of the two lesions. In particular we evidence a very limited structural deformation induced by CPD while 64-PP is characterized by a complex structural polymorphism...
February 28, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334797/molecular-mechanism-governing-ratio-dependent-transcription-regulation-in-the-ccdab-operon
#8
Alexandra Vandervelde, Igor Drobnak, San Hadži, Yann G-J Sterckx, Thomas Welte, Henri De Greve, Daniel Charlier, Rouslan Efremov, Remy Loris, Jurij Lah
Bacteria can become transiently tolerant to several classes of antibiotics. This phenomenon known as persistence is regulated by small genetic elements called toxin-antitoxin modules with intricate yet often poorly understood self-regulatory features. Here, we describe the structures of molecular complexes and interactions that drive the transcription regulation of the ccdAB toxin-antitoxin module. Low specificity and affinity of the antitoxin CcdA2 for individual binding sites on the operator are enhanced by the toxin CcdB2, which bridges the CcdA2 dimers...
February 17, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334526/an-unusual-non-emissive-behavior-of-rubrene-j-aggregates-a-rare-violation
#9
Nikhil Aggarwal, Archita Patnaik
Structure - property correlations in Rubrene (RB) colloidal J-aggregates were unravelled by steady state and time resolved spectroscopy in conjunction with excited state density functional calculations. The RB J-aggregate with a slippage angle θ = 30.4(0), estimated from the monomeric transition dipole moment directions, exhibited a broad FWHM of 1073 cm(-1) and a 5 nm red shifted absorption band carrying a transition dipole moment (M ⃗_(λagg )= 1.80 D) almost equivalent to the monomeric dye (M ⃗_(λmon )=1...
March 23, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28333549/ksr-as-a-therapeutic-target-for-ras-dependent-cancers
#10
Beth K Neilsen, Danielle E Frodyma, Robert E Lewis, Kurt W Fisher
Targeting downstream effectors required for oncogenic Ras signaling is a potential alternative or complement to the development of more direct approaches targeting Ras in the treatment of Ras-dependent cancers. Areas covered: Here we review literature pertaining to the molecular scaffold Kinase Suppressor of Ras (KSR) and its role in promoting signals critical to tumor maintenance. We summarize the phenotypes in knockout models, describe the role of KSR in cancer, and outline the structure and function of the KSR1 and KSR2 proteins...
March 23, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28333462/lattice-solvent-effects-in-the-spin-crossover-of-an-fe-ii-based-material-the-key-role-of-intermolecular-interactions-between-solvent-molecules
#11
Maria Fumanal, Fernando Jiménez-Grávalos, Jordi Ribas-Arino, Sergi Vela
The spin transition of Fe(II) complexes is the subject of intensive synthetic and computational efforts. In this manuscript, we analyze the spin crossover (SCO) of [Fe(E-dpsp)2](2+) (1), which features a spin transition depending on the cocrystallizing solvent molecules. Whereas the use of acetone results in a hysteretic spin transition at ∼170 K, the use of propylene carbonate (PC) results in a permanent diamagnetic signal up to 300 K. By means of DFT+U+D2 calculations in the solid state of the material, we unravel the reasons for such different behavior...
March 23, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28333451/aerosol-formation-from-oh-oxidation-of-the-volatile-cyclic-methyl-siloxane-cvms-decamethylcyclopentasiloxane
#12
Yue Wu, Murray V Johnston
Aerosol formation from OH oxidation of decamethylcyclopentasiloxane (D5, C10H30O5Si5), a cyclic volatile methyl siloxane (cVMS) found in consumer products, was studied in a flow-through photo chamber with and without the presence of ammonium sulfate seed aerosol. For the unseeded experiments, chemical characterization with high performance mass spectrometry showed that the molecular composition changed substantially with aerosol mass loading in the 1-12 μg/m3 range. Monomers (5 Si atoms/molecule) and dimers (10 Si atoms/molecule) dominated the mass spectra of aerosols at higher mass loadings while ring opened species (neither 5 nor 10 Si atoms/molecule) dominated the mass spectra of aerosols at lower mass loadings...
March 23, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28333212/structural-history-of-human-srgap2-proteins
#13
Michael Sporny, Julia Guez-Haddad, Annett Kreusch, Sivan Shakartzi, Avi Neznansky, Alice Cross, Michail N Isupov, Britta Qualmann, Michael M Kessels, Yarden Opatowsky
In the development of the human brain, human-specific genes are considered to play key roles, conferring its unique advantages and vulnerabilities. At the time of Homo lineage divergence from Australopithecus, SRGAP2C gradually emerged through a process of serial duplications and mutagenesis from ancestral SRGAP2A (3.4-2.4 Ma). Remarkably, ectopic expression of SRGAP2C endows cultured mouse brain cells, with human-like characteristics, specifically, increased dendritic spine length and density. To understand the molecular mechanisms underlying this change in neuronal morphology, we determined the structure of SRGAP2A and studied the interplay between SRGAP2A and SRGAP2C...
February 21, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/28333095/cytosolic-bnip3-dimer-interacts-with-mitochondrial-bax-forming-heterodimers-in-the-mitochondrial-outer-membrane-under-basal-conditions
#14
Ulrike B Hendgen-Cotta, Sonja Esfeld, Katharina Rudi, Ilkka Miinalainen, Johann P Klare, Tienush Rassaf
The primary function of mitochondria is energy production, a task of particular importance especially for cells with a high energy demand like cardiomyocytes. The B-cell lymphoma (BCL-2) family member BCL-2 adenovirus E1B 19 kDa-interacting protein 3 (BNIP3) is linked to mitochondrial targeting after homodimerization, where it functions in inner membrane depolarization and permeabilization of the mitochondrial outer membrane (MOM) mediating cell death. We investigated the basal distribution of cardiac BNIP3 in vivo and its physical interaction with the pro-death protein BCL2 associated X, apoptosis regulator (BAX) and with mitochondria using immunoblot analysis, co-immunoprecipitation, and continuous wave and pulsed electron paramagnetic resonance spectroscopy techniques...
March 23, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28332842/generation-of-antifungal-stilbenes-using-the-enzymatic-secretome-of-botrytis-cinerea
#15
Katia Gindro, Sylvain Schnee, Davide Righi, Laurence Marcourt, Samad Nejad Ebrahimi, Josep Massana Codina, Francine Voinesco, Emilie Michellod, Jean-Luc Wolfender, Emerson Ferreira Queiroz
The protein secretome of Botrytis cinerea was used to perform the biotransformation of resveratrol, pterostilbene, and a mixture of both. Metabolite profiling by UHPLC-HRMS revealed the presence of compounds with unusual molecular formula, suggesting the existence of new products. To isolate these products, the reactions were scaled-up, and 21 analogues were isolated and fully characterized by NMR and HRESIMS analyses. The reaction with pterostilbene afforded five new compounds, while the reaction with a mixture of pterostilbene and resveratrol afforded seven unusual stilbene dimers...
March 23, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28332749/bioinspired-asymmetric-synthesis-of-hispidanin%C3%A2-a
#16
Fuzhuo Li, Qian Tu, Sijia Chen, Lei Zhu, Yu Lan, Jianxian Gong, Zhen Yang
The first enantiospecific synthesis of hispidanin A (4), a dimeric diterpenoid from the rhizomes of Isodon hispida, was achieved with a longest linear sequence of 12 steps in 6.5 % overall yield. A key component is the use of the abundant and naturally occurring diterpenoids (+)-sclareolide and (+)-sclareol as starting materials, which enables the gram-scale preparation of the key intermediates totarane (1) and s-trans-12E,14-labdadien-20,8β-olide (2). Subsequently a thermal or an erbium-catalyzed intermolecular Diels-Alder reaction of totarane (1) with labdadienolide (2) provide convergent and rapid access to the natural product hispidanin A (4)...
March 23, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28332702/the-mtp1-promoters-from-arabidopsis-halleri-reveal-cis-regulating-elements-for-the-evolution-of-metal-tolerance
#17
Elisa Fasani, Giovanni DalCorso, Claudio Varotto, Mingai Li, Giovanna Visioli, Monica Mattarozzi, Antonella Furini
In the hyperaccumulator Arabidopsis halleri, the zinc (Zn) vacuolar transporter MTP1 is a key component of hypertolerance. Because protein sequences and functions are highly conserved between A. halleri and Arabidopsis thaliana, Zn tolerance in A. halleri may reflect the constitutively higher MTP1 expression compared with A. thaliana, based on copy number expansion and different cis regulation. Three MTP1 promoters were characterized in A. halleri ecotype I16. The comparison with the A. thaliana MTP1 promoter revealed different expression profiles correlated with specific cis-acting regulatory elements...
March 23, 2017: New Phytologist
https://www.readbyqxmd.com/read/28332684/dft-calculations-as-a-ligand-toolbox-for-the-synthesis-of-active-initiators-for-rop-of-cyclic-esters
#18
D Jędrzkiewicz, D Kantorska, J Wojtaszak, J Ejfler, S Szafert
New heteroleptic zinc dimeric complexes bearing an aminophenolate ligand of a single-site initiator framework were synthesized and characterized by spectroscopic methods, X-ray analysis, and DFT calculations. The theoretical study, verified by the experimental data, explains the catalytic behaviour in the ROP of lactide in the examined zinc complexes. The presented simple DFT protocol constitutes a valuable method for the qualification of the ancillary ligand to rationally design new complexes to improve their catalytic activity...
March 23, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/28332352/development-of-inhibitors-targeting-hypoxia-inducible-factor-1-and-2-for-cancer-therapy
#19
REVIEW
Tianchi Yu, Bo Tang, Xueying Sun
Hypoxia is frequently observed in solid tumors and also one of the major obstacles for effective cancer therapies. Cancer cells take advantage of their ability to adapt hypoxia to initiate a special transcriptional program that renders them more aggressive biological behaviors. Hypoxia-inducible factors (HIFs) are the key factors that control hypoxia-inducible pathways by regulating the expression of a vast array of genes involved in cancer progression and treatment resistance. HIFs, mainly HIF-1 and -2, have become potential targets for developing novel cancer therapeutics...
May 2017: Yonsei Medical Journal
https://www.readbyqxmd.com/read/28332148/ph-dependent-structural-modulation-is-conserved-in-the-human-small-heat-shock-protein-hsbp1
#20
Amanda F Clouser, Rachel E Klevit
The holdase activity and oligomeric propensity of human small heat shock proteins (sHSPs) are regulated by environmental factors. However, atomic-level details are lacking for the mechanisms by which stressors alter sHSP responses. We previously demonstrated that regulation of HSPB5 is mediated by a single conserved histidine over a physiologically relevant pH range of 6.5-7.5. Here, we demonstrate that HSPB1 responds to pH via a similar mechanism through pH-dependent structural changes that are induced via protonation of the structurally analogous histidine...
March 22, 2017: Cell Stress & Chaperones
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