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https://www.readbyqxmd.com/read/29341887/molecular-basis-of-substrate-polyspecificity-of-the-candida-albicans-mdr1p-multidrug-h-antiporter
#1
Archana Kumari Redhu, Atanu Banerjee, Abdul Haseeb Shah, Alexis Moreno, Manpreet Kaur Rawal, Remya Nair, Pierre Falson, Rajendra Prasad
The molecular basis of polyspecificity of Mdr1p, a major drug/H+ antiporter of Candida albicans, is not elucidated. We have probed the nature of the drug-binding pocket by performing systematic mutagenesis of the 12 transmembrane segments. Replacement of the 252 amino acid residues with alanine or glycine yielded 2/3 neutral mutations while 1/3 led to the complete or selective lost of resistance to drugs or substrates transported by the pump. Using the GlpT-based 3D-model of Mdr1p, we roughly categorized these critical residues depending on their type and localization 1°/ main structural impact ("S" group), 2°/ exposure to the lipid interface ("L" group), 3°/ buried but not facing the main central pocket, inferred as critical for the overall H+/drug antiport mechanism ("M" group) and finally 4°/ buried and facing the main central pocket ("B" group)...
January 13, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29340380/a-dft-study-of-the-adsorption-of-short-peptides-on-mg-and-mg-based-alloy-surfaces
#2
Zhe Fang, Jianfeng Wang, Shijie Zhu, Xiaofan Yang, Yu Jia, Qiang Sun, Shaokang Guan
Adsorption of short peptides, including three dipeptides: arginine-glycine (Arg-Gly), glycine-aspartic acid (Gly-Asp), arginine-aspartic acid (Arg-Asp), and one tripeptide arginine-glycine-aspartic acid (RGD), on the surfaces of Mg and Mg alloys (Mg-Zn, Mg-Y, and Mg-Nd), was studied using the first-principles calculations based on density functional theory (DFT), considering van der Waals (vdW) correction. The calculated adsorption energies (Eads) of short peptides on the clean Mg(0001) surface are in the range of -1...
January 17, 2018: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/29340233/crustacean-amphipods-from-marsh-ponds-a-nutritious-feed-resource-with-potential-for-application-in-integrated-multi-trophic-aquaculture
#3
Pablo Jiménez-Prada, Ismael Hachero-Cruzado, Inmaculada Giráldez, Catalina Fernández-Diaz, César Vilas, José Pedro Cañavate, José Manuel Guerra-García
Coastal protection, nutrient cycling, erosion control, water purification, and carbon sequestration are ecosystem services provided by salt marshes. Additionally, salt ponds offer coastal breeding and a nursery habitat for fishes and they provide abundant invertebrates, such as amphipods, which are potentially useful as a resource in aquaculture. Fishmeal and fish oil are necessary food resources to support aquaculture of carnivorous species due to their omega-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA)...
2018: PeerJ
https://www.readbyqxmd.com/read/29339506/development-and-retention-of-a-primordial-moonlighting-pathway-of-protein-modification-in-the-absence-of-selection-presents-a-puzzle
#4
Xinyun Cao, Yaoqin Hong, Lei Zhu, Yuanyuan Hu, John E Cronan
Lipoic acid is synthesized by a remarkably atypical pathway in which the cofactor is assembled on its cognate proteins. An octanoyl moiety diverted from fatty acid synthesis is covalently attached to the acceptor protein, and sulfur insertion at carbons 6 and 8 of the octanoyl moiety form the lipoyl cofactor. Covalent attachment of this cofactor is required for function of several central metabolism enzymes, including the glycine cleavage H protein (GcvH). In Bacillus subtilis, GcvH is the sole substrate for lipoate assembly...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29339156/structure-and-function-of-cytoplasmic-serine-hydroxymethyltransferase-from-pichia-pastoris
#5
Manfeng Zhang, Wei Wu, Zhongzhou Chen
Serine hydroxymethyltransferase (SHMT) catalyzes the interconversion of serine and glycine, which is crucial for one carbon metabolism. Here, we report the first crystal structure of cytoplasmic SHMT from Pichia pastoris (pcSHMT) diffracted to 2.5 Å resolution in space group C2221. PcSHMT was a contaminant with our target protein expressed in Pichia pastoris and confirmed by mass spectrometry. The overall structure of pcSHMT is similar to Human mitochondrial SHMT and different to E. coli SHMT. Interestingly, the oligomerization of pcSHMT expressed in eukaryotic or prokaryotic system differs significantly and is regulated by pyridoxal-5'-phosphate...
January 12, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29338614/the-two-mutations-of-actin-myosin-interface-and-their-effect-on-the-dynamics-structures-and-functions-of-skeletal-muscle-actin
#6
Faeze Sadat Mohajer, Sepideh Parvizpour, Jafar Razmara, Mohd Shahir Shamsir
Congenital myopathy is a broad category of muscular diseases with symptoms appearing at the time of birth. One type of congenital myopathy is Congenital Fiber Type Disproportion (CFTD), a severely debilitating disease. The G48D and G48C mutations in the D-loop and the actin-myosin interface are the two causes of CFTD. These mutations have been shown to significantly affect the structure and function of muscle fibers. To the author's knowledge, the effects of these mutations have not yet been studied. In this work, the power stroke structure of the head domain of myosin and the wild and mutated types of actin were modeled...
January 17, 2018: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/29338548/glycine-transporter-1-inhibitors-a-patent-review-2011-2016
#7
Christopher L Cioffi
Numerous research groups have developed GlyT-1 inhibitors in the pursuit of providing a novel antipsychotic treatment for schizophrenia. Despite multiple compounds advancing into clinical trials, a GlyT-1 inhibitor has yet to emerge to treat patients. However, the approach remains heavily investigated as it presents potential therapeutic utility for several other CNS and non-CNS-related indications. Areas covered: This review discusses various GlyT-1 inhibitor chemotypes identified and provides an overview of patent applications filed and published during the period of 2011-2016...
January 17, 2018: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/29338542/the-novel-microtubule-associated-cap-glycine-protein-cgp1-governs-growth-differentiation-and-virulence-of-cryptococcus-neoformans
#8
Li Li Wang, Kyung-Tae Lee, Kwang-Woo Jung, Dong-Gi Lee, Yong-Sun Bahn
Microtubules are involved in mechanical support, cytoplasmic organization, and several cellular processes by interacting with diverse microtubule-associated proteins such as plus-end tracking proteins, motor proteins, and tubulin-folding cofactors. A number of the cytoskeleton-associated proteins (CAPs) contain the CAP-glycine-rich (CAP-Gly) domain, which is evolutionarily conserved and generally considered to bind to α-tubulin to regulate the function of microtubules. However, there has been a dearth of research on CAP-Gly proteins in fungal pathogens, including Cryptococcus neoformans, which is a global cause of fatal meningoencephalitis in immunocompromised patients...
January 17, 2018: Virulence
https://www.readbyqxmd.com/read/29335837/backbone-chemical-shift-assignments-of-the-glycine-cleavage-complex-h-protein-of-escherichia-coli
#9
Usha Yadav, Monica Sundd
Glycine cleavage complex H protein (GcvH) is one of the four components that form the glycine cleavage complex (GCS), essential for the synthesis of C1 (one-carbon units) for cell metabolism, by the oxidative cleavage of glycine. The activity of this complex is induced in the presence of exogenous glycine, and is repressed by purines. GCS, in cooperation with GCA (serine hydroxymethyltransferase) regulates the endogenous levels of glycine and C1 units in the cell. GcvH, the lipoamide containing component of the complex, plays an indispensable role in this reaction, as its prosthetic group shuttles between the active site of the three other components of the GCS complex sequentially...
January 15, 2018: Biomolecular NMR Assignments
https://www.readbyqxmd.com/read/29335813/organic-acidurias-in-adults-late-complications-and-management
#10
Ali Tunç Tuncel, Nikolas Boy, Marina A Morath, Friederike Hörster, Ulrike Mütze, Stefan Kölker
Organic acidurias (synonym, organic acid disorders, OADs) are a heterogenous group of inherited metabolic diseases delineated with the implementation of gas chromatography/mass spectrometry in metabolic laboratories starting in the 1960s and 1970s. Biochemically, OADs are characterized by accumulation of mono-, di- and/or tricarboxylic acids ("organic acids") and corresponding coenzyme A, carnitine and/or glycine esters, some of which are considered toxic at high concentrations. Clinically, disease onset is variable, however, affected individuals may already present during the newborn period with life-threatening acute metabolic crises and acute multi-organ failure...
January 15, 2018: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/29334413/features-of-auxiliaries-that-enable-native-chemical-ligation-beyond-glycine-and-cleavage-via-radical-fragmentation
#11
Simon Ferdinand Loibl, Andre Dallmann, Kathleen Hennig, Carmen Juds, Oliver Seitz
The native chemical ligation (NCL) is an invaluable tool in the total chemical synthesis of proteins. Ligation auxiliaries overcome the requirement for cysteine. However, the reported auxiliaries remained limited to glycine-containing ligation sites and the acidic conditions applied for cleavage of the typically applied N-benzyl-type linkages promote side reactions. With the aim to improve upon both ligation and cleavage, we systematically investigated alternative ligation scaffolds that challenge the N-benzyl dogma...
January 15, 2018: Chemistry: a European Journal
https://www.readbyqxmd.com/read/29333938/structure-based-engineering-to-restore-high-affinity-binding-of-an-isoform-selective-anti-tgf%C3%AE-1-antibody
#12
Dana M Lord, Julie J Bird, Denise M Honey, Annie Best, Anna Park, Ronnie R Wei, Huawei Qiu
Metelimumab (CAT192) is a human IgG4 monoclonal antibody developed as a TGFβ1-specific antagonist. It was tested in clinical trials for the treatment of scleroderma but later terminated due to lack of efficacy. Subsequent characterization of CAT192 indicated that its TGFβ1 binding affinity was reduced by ∼50-fold upon conversion from the parental single-chain variable fragment (scFv) to IgG4. We hypothesized this result was due to decreased conformational flexibility of the IgG that could be altered via engineering...
January 15, 2018: MAbs
https://www.readbyqxmd.com/read/29333856/analysis-of-the-ph-dependent-fe-iii-ion-chelating-activity-of-anthocyanin-extracted-from-black-soybean-glycine-max-l-merr-coats
#13
Yanli Xie, Xiaolu Zhu, Yuan Li, Cheng Wang
The Fe(III) chelating activity of anthocyanin extracted from black soybean coats was investigated at pH 3.0, 5.0, 6.5, 7.0 and 7.4 with fluorescence spectroscopy and microscale thermophoresis (MST). Cyanidin-3-glucoside (C3G) was determined to be 98% of the total anthocyanin by HPLC. The binding affinity (Ka) exhibited significant pH-dependent behavior; Ka was 9.7167, 1.0837, 1.4284, 5.4550 and 3.0269×104 M-1 at pH 3.0, 5.0, 6.5, 7.0 and 7.4, respectively (p<0.05). The MST data showed that ΔG<0 and ΔH<0, demonstrating that chelation is spontaneous and exothermic...
January 15, 2018: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29333573/simultaneous-site-directed-mutagenesis-of-duplicated-loci-in-soybean-using-a-single-guide-rna
#14
Yuhei Kanazashi, Aya Hirose, Ippei Takahashi, Masafumi Mikami, Masaki Endo, Sakiko Hirose, Seiichi Toki, Akito Kaga, Ken Naito, Masao Ishimoto, Jun Abe, Tetsuya Yamada
Using a gRNA and Agrobacterium-mediated transformation, we performed simultaneous site-directed mutagenesis of two GmPPD loci in soybean. Mutations in GmPPD loci were confirmed in at least 33% of T2 seeds. The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated endonuclease 9 (Cas9) system is a powerful tool for site-directed mutagenesis in crops. Using a single guide RNA (gRNA) and Agrobacterium-mediated transformation, we performed simultaneous site-directed mutagenesis of two homoeologous loci in soybean (Glycine max), GmPPD1 and GmPPD2, which encode the orthologs of Arabidopsis thaliana PEAPOD (PPD)...
January 15, 2018: Plant Cell Reports
https://www.readbyqxmd.com/read/29331845/effect-of-levetiracetam-on-extracellular-amino-acid-levels-in-the-dorsal-hippocampus-of-rats-with-temporal-lobe-epilepsy
#15
Pichardo Macías Luz Adriana, Ramírez Mendiola Blanca Alcira, Contreras García Itzel Jatziri, Zamudio Hernández Sergio Roberto, Chávez Pacheco Juan Luis, Sánchez Huerta Karla Berenice, Mendoza Torreblanca Julieta Griselda
Levetiracetam (LEV) is an anticonvulsant drug with a unique mechanism of action that is not completely understood. However, its activity profile may involve effects on excitatory and/or inhibitory neurotransmission since the primary target of LEV, synaptic vesicle protein 2A, is ubiquitously expressed in all types of synaptic vesicles. Therefore, the objective of the present study was to explore the effect of LEV (300 mg/kg/day for one week, administered via osmotic mini-pumps) on neurotransmitter release and its probable selective effect on extracellular gamma-amino butyric acid (GABA), glutamate (Glu), aspartate (Asp), glutamine (Gln), taurine (Tau) and glycine (Gly) concentrations (using in vivo microdialysis under basal and high-K+ conditions) in the dorsal hippocampus (DH), a region that undergoes major synaptic changes during epilepsy...
January 5, 2018: Epilepsy Research
https://www.readbyqxmd.com/read/29331591/brochosomins-and-other-novel-proteins-from-brochosomes-of-leafhoppers-insecta-hemiptera-cicadellidae
#16
Roman Rakitov, Alexander A Moysa, Arthur T Kopylov, Sergei A Moshkovskii, Ralph S Peters, Karen Meusemann, Bernhard Misof, Christopher H Dietrich, Kevin P Johnson, Lars Podsiadlowski, Kimberly K O Walden
Brochosomes (BS) are secretory granules resembling buckyballs, produced intracellularly in specialized glandular segments of the Malpighian tubules and forming superhydrophobic coatings on the integuments of leafhoppers (Hemiptera, Cicadellidae). Their composition is poorly known. Using a combination of SDS-PAGE, LC-MS/MS, next-generation sequencing (RNAseq) and bioinformatics we demonstrate that the major structural component of BS of the leafhopper Graphocephala fennahi Young is a novel family of 21-40-kDa secretory proteins, referred to herein as brochosomins (BSM), apparently cross-linked by disulfide bonds...
January 10, 2018: Insect Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/29331136/zwitterionization-of-glycine-in-water-environment-stabilization-mechanism-and-nmr-spectral-signatures
#17
Danillo Valverde, Zélia Maria da Costa Ludwig, Célia Regina da Costa, Valdemir Ludwig, Herbert C Georg
At physiological conditions, myriads of biomolecules (e.g., amino acids, peptides, and proteins) exist predominantly in the zwitterionic structural form and their biological functions will result in these conditions. However these geometrical structures are inaccessible energetically in the gas phase, and at this point, stabilization of amino-acids in physiological conditions is still under debate. In this paper, the electronic properties of a glycine molecule in the liquid environment were studied by performing a relaxation of the glycine geometry in liquid water using the free energy gradient method combined with a sequential quantum mechanics/molecular mechanics approach...
January 14, 2018: Journal of Chemical Physics
https://www.readbyqxmd.com/read/29330582/nano-silicon-alters-antioxidant-activities-of-soybean-seedlings-under-salt-toxicity
#18
Salar Farhangi-Abriz, Shahram Torabian
Materials with a particle size less than 100 nm are classified as nano-materials. The physical and chemical properties of nano-materials can vary considerably from those of bulk materials of the same composition. Silicon (Si) still fails to get recognized as an essential nutrient for plant growth and development, however the beneficial effects in terms of growth, biotic and abiotic stress resistance have been indicated in a variety of plant species for their growth. The aim of this study was to investigate the effects of different nano-silicon rates on the growth and antioxidant activities of soybean (Glycine max L...
January 12, 2018: Protoplasma
https://www.readbyqxmd.com/read/29330292/microenvironmental-derived-regulation-of-hif-signaling-drives-transcriptional-heterogeneity-in-glioblastoma-multiforme
#19
Dieter Henrik Heiland, Annette Gaebelein, Melanie Boerries, Jakob Woerner, Nils Pompe, Pamela Franco, Sabrina Heynckes, Mark D Bartholomä, Darren Ó hAilín, Maria Stella Carro, Marco Prinz, Stefan Weber, Irina Mader, Daniel Delev, Oliver Schnell
The evolving and highly heterogeneous nature of malignant brain tumors underlies their limited response to therapy and poor prognosis. In addition to genetic alterations, highly dynamic processes such as transcriptional and metabolic reprogramming play an important role in the development of tumor heterogeneity. The present study reports an adaptive mechanism in which the metabolic environment of malignant glioma drives transcriptional reprogramming. Multi-regional analysis of a glioblastoma patient biopsy revealed a metabolic landscape marked by varying stages of hypoxia and creatine enrichment...
January 12, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29330177/incidence-of-facultative-bacterial-endosymbionts-in-spider-mites-associated-with-local-environment-and-host-plant
#20
Yu-Xi Zhu, Yue-Ling Song, Yan-Kai Zhang, Ary A Hoffmann, Jin-Cheng Zhou, Jing-Tao Sun, Xiao-Yue Hong
Spider mites are frequently associated with multiple endosymbionts whose infection patterns often exhibit spatial and temporal variation. However, the association between endosymbiont prevalence and environmental factors remains unclear. Here, we surveyed endosymbionts in natural populations of the spider mite, Tetranychus truncatus, in China, screening 935 spider mites from 21 localities and 12 host plant species. Three facultative endosymbiont lineages, Wolbachia, Cardinium, and Spiroplasma, were detected at different infection frequencies (52...
January 12, 2018: Applied and Environmental Microbiology
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