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https://www.readbyqxmd.com/read/28800624/destabilizing-polymorphism-in-cervid-prion-protein-hydrophobic-core-determines-prion-conformation-and-conversion-efficiency
#1
Samia Hannaoui, Sara Amidian, Yo Ching Cheng, Camilo Duque Velásquez, Lyudmyla Dorosh, Sampson Law, Glenn Telling, Maria Stepanova, Debbie McKenzie, Holger Wille, Sabine Gilch
Prion diseases are infectious neurodegenerative disorders of humans and animals caused by misfolded forms of the cellular prion protein PrPC. Prions cause disease by converting PrPC into aggregation-prone PrPSc. Chronic wasting disease (CWD) is the most contagious prion disease with substantial lateral transmission, affecting free-ranging and farmed cervids. Although the PrP primary structure is highly conserved among cervids, the disease phenotype can be modulated by species-specific polymorphisms in the prion protein gene...
August 11, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28797801/dimeric-and-trimeric-homo-and-heteroleptic-hydroxamic-acid-macrocycles-formed-using-mixed-ligand-fe-iii-based-metal-templated-synthesis
#2
Athavan Sresutharsan, William Tieu, Tomas Richardson-Sanchez, Cho Zin Soe, Rachel Codd
Macrocyclic hydroxamic acids coordinate Fe(III) with high affinity as part of siderophore-mediated bacterial iron acquisition. Trimeric hydroxamic acid macrocycles, such as desferrioxamine E (DFOE), are prevalent in nature, with fewer dimeric macrocycles identified, including putrebactin (pbH2), avaroferrin (avH2), bisucaberin (bsH2) and alcaligin (alH2). This work used metal-templated synthesis (MTS) to pre-assemble complexes between one equivalent of Fe(III) and two equivalents of 4-((4-aminobutyl)(hydroxy)amino)-4-oxobutanoic acid (BBH) or 4-((5-aminopentyl)(hydroxy)amino)-4-oxobutanoic acid (PBH)...
August 1, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28792212/the-lc8-recognition-motif-preferentially-samples-polyproline-ii-structure-in-its-free-state
#3
Jessica Morgan, Malene Ringkjøbing Jensen, Valéry Ozenne, Martin Blackledge, Elisar J Barbar
LC8 is a ubiquitous hub protein that binds intrinsically disordered proteins and promotes their assembly into higher order complexes. A common feature among the over 100 essential LC8-binding proteins is that in the 10-12 amino acid recognition sequence there is a conserved QT motif but variable amino acids N- and C-terminal to the QT pair. The sequence diversity among LC8-binding partners implies that structural factors also contribute to specificity. To investigate whether one such factor is the transient secondary structure favored by an LC8-binding sequence, we report here a molecular ensemble description of ICTL, a domain of dynein intermediate chain that includes binding sites for light chains LC8 and Tctex1...
August 9, 2017: Biochemistry
https://www.readbyqxmd.com/read/28791742/a-multispecific-monoclonal-antibody-g2-recognizes-at-least-three-completely-different-epitope-sequences-with-high-affinity
#4
Md Nuruddin Mahmud, Masayuki Oda, Daiki Usui, Yasuo Inoshima, Naotaka Ishiguro, Yuji O Kamatari
A monoclonal antibody (mAb) G2 possesses an unusual characteristic of reacting with at least three proteins (ATP6V1C1, SEPT3, and C6H10orf76) other than its original antigen, chicken prion protein (ChPrP). The epitopes on ChPrP and ATP6V1C1 have been identified previously. In this study, we identified the epitope in the third protein, SEPT3. Interestingly, there was no amino acid sequence similarity among the epitopes on the three proteins. These epitopes had high binding affinities to G2 (KD = ∼10(-7) M for monovalent binding and KD = ∼10(-9) M for divalent binding), as determined using a SPR biosensor...
August 9, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28751905/monoterpenyl-glycosyltransferases-differentially-contribute-to-production-of-monoterpenyl-glycosides-in-two-aromatic-vitis-vinifera-varieties
#5
Xiang-Yi Li, Ya-Qin Wen, Nan Meng, Xu Qian, Qiu-Hong Pan
HIGHLIGHTS A similar trend on accumulation of glycosidically bound monoterpenes was observed in both varietiesTwo VvGT7 alleles mutations occurred at key sites in Muscat blanc à PetitVvGT14 exerted a major role in production of monoterpenyl glycosides in both varieties Terpenoids are the major aroma components and generally exist as both free and glycosidically-bound forms, of which nonvolatile glycosides account for a large fraction in grape berries. Our previous study has indicated that differential accumulation of monoterpenyl glycosides in Vitis vinifera "Muscat blanc à Petit" between two regions is closely correlated to monoterpenyl glucosyltransferase (VvGT14, XM_002285734...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28745873/physiological-concentrations-of-ascorbate-cannot-prevent-the-potentially-damaging-reactions-of-protein-radicals-in-humans
#6
Thomas Nauser, Janusz Gebicki
The principal initial biological targets of free radicals formed under condition of oxidative stress are the proteins. The most common product of the interaction are carbon-centered alkyl radicals which react rapidly with oxygen to form peroxyl radicals and hydroperoxides. All these species are reactive, capable of propagating the free radical damage to enzymes, nucleic acids, lipids and endogenous antioxidants, leading finally to the pathologies associated with oxidative stress. The best chance of preventing this chain of damage is in early repair of the protein radicals by antioxidants...
July 26, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28739800/cell-free-production-of-a-functional-oligomeric-form-of-a-chlamydia-major-outer-membrane-protein-momp-for-vaccine-development
#7
Wei He, Martina Felderman, Angela C Evans, Jia Geng, David Homan, Feliza Bourguet, Nicholas O Fischer, Yuanpei Li, Kit S Lam, Aleksandr Noy, Li Xing, R Holland Cheng, Amy Rasley, Craig D Blanchette, Kurt Kamrud, Nathanial Wang, Heather Gouvis, Todd C Peterson, Bolyn Hubby, Matthew A Coleman
Chlamydia is a prevalent sexually transmitted disease that infects more than 100 million people worldwide. Although most individuals infected with Chlamydia trachomatis are initially asymptomatic, symptoms can arise if left undiagnosed. Long-term infection can result in debilitating conditions such as pelvic inflammatory disease, infertility, and blindness. Chlamydia infection, therefore, constitutes a significant public health threat, underscoring the need for a Chlamydia-specific vaccine. Chlamydia strains express a major outer-membrane protein (MOMP) that has been shown to be an effective vaccine antigen...
July 24, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28737807/npy-binds-with-heme-to-form-a-npy-heme-complex-enhancing-peroxidase-activity-in-free-heme-and-promoting-npy-nitration-and-inactivation
#8
Huixian Ye, Zhen Yang, Hailing Li, Zhonghong Gao
Neuropeptide Y (NPY) is a member of the pancreatic peptide family of neuropeptides that play a crucial role in numerous central and peripheral nervous system responses. Recently, it has been shown that NPY protects cells against neurotoxic damage from β-amyloid peptides (Aβ) in Alzheimer's disease (AD). Heme is a common factor linking several metabolic perturbations in AD and altered heme metabolism has been shown to be related to the pathologies of AD. Thus, heme may have a chance to act on NPY and potentially counteract its function...
July 24, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/28729559/effects-of-poly-%C3%AE-glutamic-acid-%C3%AE-pga-on-plant-growth-and-its-distribution-in-a-controlled-plant-soil-system
#9
Lei Zhang, Xueming Yang, Decai Gao, Lingli Wang, Jie Li, Zhanbo Wei, Yuanliang Shi
To demonstrate the responses of plant (Pakchoi) and soil to poly-γ-glutamic acid (γ-PGA) is essential to better understand the pathways of the promotional effect of γ-PGA on plant growth. In this study, the effects of γ-PGA on soil nutrient availability, plant nutrient uptake ability, plant metabolism and its distribution in a plant-soil system were tested using labeled γ-PGA synthesized from (13)C1-(15)N-L-glutamic acid (L-Glu). γ-PGA significantly improved plant uptake of nitrogen (N), phosphorus (P), and potassium (K) and hence increased plant biomass...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28729386/dormancy-in-embryos-insight-from-hydrated-encysted-embryos-of-an-aquatic-invertebrate
#10
Tamar Ziv, Vered Chalifa-Caspi, Nadav Denekamp, Inbar Plaschkes, Sylwiya Sylwia Kierszniowska, Idit Blais, Arie Admon, Esther Lubzens
Numerous aquatic invertebrates remain dormant for decades in a hydrated state as encysted embryos. In search for functional pathways associated with this form of dormancy, we used label-free quantitative proteomics to compare the proteomes of hydrated encysted dormant embryos (resting eggs; RE) with non-dormant embryos (amictic eggs; AM) of the rotifer Brachionus plicatilis</p> <p>A total of 2,631 proteins were identified in rotifer eggs. About 62% proteins showed higher abundance in AM relative to RE (Fold Change>3; p=0...
July 20, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28723955/crystal-structure-and-functional-characterization-of-an-isoaspartyl-dipeptidase-cpsiada-from-colwellia-psychrerythraea-strain-34h
#11
Sun-Ha Park, Chang Woo Lee, Sung Gu Lee, Seung Chul Shin, Hak Jun Kim, Hyun Park, Jun Hyuck Lee
Isoaspartyl dipeptidase (IadA) is an enzyme that catalyzes the hydrolysis of an isoaspartyl dipeptide-like moiety, which can be inappropriately formed in proteins, between the β-carboxyl group side chain of Asp and the amino group of the following amino acid. Here, we have determined the structures of an isoaspartyl dipeptidase (CpsIadA) from Colwellia psychrerythraea, both ligand-free and that complexed with β-isoaspartyl lysine, at 1.85-Å and 2.33-Å resolution, respectively. In both structures, CpsIadA formed an octamer with two Zn ions in the active site...
2017: PloS One
https://www.readbyqxmd.com/read/28723063/using-cooperatively-folded-peptides-to-measure-interaction-energies-and-conformational-propensities
#12
Maziar S Ardejani, Evan T Powers, Jeffery W Kelly
The rates and equilibria of the folding of biopolymers are determined by the conformational preferences of the subunits that make up the sequence of the biopolymer and by the interactions that are formed in the folded state in aqueous solution. Because of the centrality of these processes to life, quantifying conformational propensities and interaction strengths is vitally important to understanding biology. In this Account, we describe our use of peptide model systems that fold cooperatively yet are small enough to be chemically synthesized to measure such quantities...
July 19, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28710924/identification-of-new-bace1-inhibitors-using-pharmacophore-and-molecular-dynamics-simulations-approach
#13
Anantha Krishnan Dhanabalan, Manish Kesherwani, Devadasan Velmurugan, Krishnasamy Gunasekaran
Inhibition of β-Secretase (BACE1) is crucial for the treatment of Alzheimer's disease (AD). Availability of BACE1 crystal structures in both apo and complexed forms enables to find structure-based BACE1 inhibitors for controlling AD. There are two catalytic aspartates (ASP32 and ASP228) presents in the active domain of BACE1. In order to understand the binding mechanism and structure-activity relationship of amidine-containing BACE1 inhibitors, molecular docking, and pharmacophore and 3D-QSAR studies have been carried out with 34 amidine derivatives to develop a pharmacophore model...
June 8, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28700717/integrated-analysis-of-zone-specific-protein-and-metabolite-profiles-within-nitrogen-fixing-medicago-truncatula-sinorhizobium-medicae-nodules
#14
Aaron J Ogden, Mahmoud Gargouri, JeongJin Park, David R Gang, Michael L Kahn
Symbiotic nitrogen fixation (SNF) between rhizobia and legumes requires metabolic coordination within specialized root organs called nodules. Nodules formed in the symbiosis between S. medicae and barrel medic (M. truncatula) are indeterminate, cylindrical, and contain spatially distinct developmental zones. Bacteria in the infection zone II (ZII), interzone II-III (IZ), and nitrogen fixation zone III (ZIII) represent different stages in the metabolic progression from free-living bacteria into nitrogen fixing bacteroids...
2017: PloS One
https://www.readbyqxmd.com/read/28697887/molecular-origins-of-the-compatibility-between-glycosaminoglycans-and-a%C3%AE-40-amyloid-fibrils
#15
Katie L Stewart, Eleri Hughes, Edwin A Yates, David A Middleton, Sheena E Radford
The Aβ peptide forms extracellular plaques associated with Alzheimer's disease. In addition to protein fibrils, amyloid plaques also contain non-proteinaceous components, including glycosaminoglycans (GAGs). We have shown previously that the GAG low-molecular-weight heparin (LMWH) binds to Aβ40 fibrils with a three-fold-symmetric (3Q) morphology with higher affinity than Aβ40 fibrils in alternative structures, Aβ42 fibrils, or amyloid fibrils formed from other sequences. Solid-state NMR analysis of the GAG-3Q fibril complex revealed an interaction site at the corners of the 3Q fibril structure, but the origin of the binding specificity remained obscure...
August 4, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28686288/distribution-of-cyp2c8-and-cyp2c9-amino-acid-substitution-alleles-in-south-indian-diabetes-patients-a-genotypic-and-computational-protein-phenotype-study
#16
Durga Koteswara Rao, Dwarakanath K Murthy, Nazia Sultana Shaik, Babajan Banaganapalli, Kumar Swami Konda, Hanumantha P Rao, Eswar Ganti, Ahmed A Zuheir, Ashraf El-Harouni, Ramu Elango, Imran Ali Khan, Noor Ahmad Shaik
The CYP2C8 and CYP2C9 are two major isoforms of the cytochrome P450 enzyme family, which is involved in drug response, detoxification, and disease development. This study describes the differential distribution of amino acid substitution variants of CYP2C8 (*2-I269F & *3-R139K) and CYP2C9 (*2-C144R & *3-L359A) genes in 234 type 2 diabetes mellitus (T2DM) patients and 218 healthy controls from Andhra Pradesh, South India. Single locus genotype analysis has revealed that homozygous recessive genotypes of 2C8*2-TT (p=<0...
July 7, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28680440/vaccatides-antifungal-glutamine-rich-hevein-like-peptides-from-vaccaria-hispanica
#17
Ka H Wong, Wei Liang Tan, Shruthi G Kini, Tianshu Xiao, Aida Serra, Sui Kwan Sze, James P Tam
Hevein and hevein-like peptides are disulfide-constrained chitin-binding cysteine-rich peptides. They are divided into three subfamilies, 6C-, 8C-, and 10C-hevein-like peptides, based on the number of cysteine residues. In addition, hevein-like peptides can exist in two forms, short and long. The long C-terminal form found in hevein and 10C-hevein-like peptides contain a C-terminal protein cargo. In contrast, the short form without a protein cargo is found in all three subfamilies. Here, we report the discovery and characterization of two novel glutamine-rich and protein cargo-free 8C-hevein-like peptides, vaccatides vH1 and vH2, from Vaccaria hispanica of the Caryophyllaceae family...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28677335/substrate-specificity-and-reaction-mechanism-of-human-prolidase
#18
Piotr Wilk, Monika Uehlein, Jacquelin Kalms, Holger Dobbek, Uwe Mueller, Manfred S Weiss
Prolidase is a ubiquitously distributed dipeptidase and the only dipeptidase in humans capable of cleaving the peptide bond preceding the amino acids proline (Pro) or hydroxyproline (Hyp). It is mainly implicated in the degradation of dietary and endogenous proteins. It is also involved in the terminal steps of collagen catabolism by hydrolyzing Pro and Hyp-containing dipeptides. Finally, it is believed to play a role in the regulation of peptidic hormones. Diminished or absent prolidase activity is related to a rare autosomal disease, referred to as prolidase deficiency (PD)...
July 4, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28676723/analysis-of-reactive-oxygen-and-nitrogen-species-generated-in-three-liquid-media-by-low-temperature-helium-plasma-jet
#19
Julie Chauvin, Florian Judée, Mohammed Yousfi, Patricia Vicendo, Nofel Merbahi
In order to identify aqueous species formed in Plasma activated media (PAM), quantitative investigations of reactive oxygen and nitrogen species (ROS, RNS) were performed and compared to Milli-Q water and culture media without and with Fetal Calf Serum. Electron paramagnetic resonance, fluorometric and colorimetric analysis were used to identify and quantify free radicals generated by helium plasma jet in these liquids. Results clearly show the formation of ROS such as hydroxyl radical, superoxide anion radical and singlet oxygen in order of the micromolar range of concentrations...
July 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28655155/evolution-of-cytochrome-c-oxidase-in-hypoxia-tolerant-sculpins-cottidae-actinopterygii
#20
Gigi Y Lau, Milica Mandic, Jeffrey G Richards
Vertebrate hypoxia tolerance can emerge from modifications to the oxygen (O2) transport cascade, but whether there is adaptive variation to O2 binding at the terminus of this cascade, mitochondrial cytochrome c oxidase (COX), is not known. In order to address the hypothesis that hypoxia tolerance is associated with enhanced O2 binding by mitochondria we undertook a comparative analysis of COX O2 kinetics across species of intertidal sculpins (Cottidae, Actinopterygii) that vary in hypoxia tolerance. Our analysis revealed a significant relationship between hypoxia tolerance (critical O2 tension of O2 consumption rate; Pcrit), mitochondrial O2 binding affinity (O2 tension at which mitochondrial respiration was half maximal; P50), and COX O2-binding affinity (apparent Michaelis-Menten constant for O2 binding to COX; Km,app O2)...
June 24, 2017: Molecular Biology and Evolution
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