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https://www.readbyqxmd.com/read/29045927/alkaline-ph-shock-enhanced-production-of-validamycin-a-in-fermentation-of-streptomyces-hygroscopicus
#1
Jing Jiang, Ya-Fang Sun, Xi Tang, Chao-Nan He, Ye-Lin Shao, Ya-Jie Tang, Wen-Wen Zhou
Validamycin A (Val-A) is produced by Streptomyces as a secondary metabolite with wide agricultural applications of controlling rice sheath blight, false smut and damping-off diseases. The effect of alkaline pH shock on enhancing Val-A production and its mechanism were investigated. A higher yield of Val-A was achieved by NaOH shock once or several times together with faster protein synthesis and sugar consumption and alkaline pH shock can increase Val-A production by 27.43%. Transcription of genes related to amino acid metabolism, carbon metabolism and electron respiratory chain was significantly up-regulated, accompanied by the substantial increase of respiratory activity and glutamate concentration...
October 6, 2017: Bioresource Technology
https://www.readbyqxmd.com/read/29045866/how-many-protein-sequences-fold-to-a-given-structure-a-coevolutionary-analysis
#2
Pengfei Tian, Robert B Best
Quantifying the relationship between protein sequence and structure is key to understanding the protein universe. A fundamental measure of this relationship is the total number of amino acid sequences that can fold to a target protein structure, known as the "sequence capacity," which has been suggested as a proxy for how designable a given protein fold is. Although sequence capacity has been extensively studied using lattice models and theory, numerical estimates for real protein structures are currently lacking...
October 17, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/29045862/the-two-state-prehensile-tail-of-the-antibacterial-toxin-colicin-n
#3
Christopher L Johnson, Alexandra S Solovyova, Olli Hecht, Colin Macdonald, Helen Waller, J Günter Grossmann, Geoffrey R Moore, Jeremy H Lakey
Intrinsically disordered regions within proteins are critical elements in many biomolecular interactions and signaling pathways. Antibacterial toxins of the colicin family, which could provide new antibiotic functions against resistant bacteria, contain disordered N-terminal translocation domains (T-domains) that are essential for receptor binding and the penetration of the Escherichia coli outer membrane. Here we investigate the conformational behavior of the T-domain of colicin N (ColN-T) to understand why such domains are widespread in toxins that target Gram-negative bacteria...
October 17, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/29045861/effects-of-nanopore-charge-decorations-on-the-translocation-dynamics-of-dna
#4
Ining Jou, Murugappan Muthukumar
We have investigated the dynamics of single-stranded DNA as it translocates through charge-mutated protein nanopores. Translocation of DNA is a crucial step in nanopore-based sequencing platforms, where control over translocation speed remains one of the main challenges. Taking advantage of the interactions between negatively charged DNA and positively charged amino acid residues, the translocation speed of DNA can be manipulated by deliberate charge decorations inside the nanopore. We employed coarse-grained Langevin dynamics simulations to monitor the step-by-step movement of DNA through different mutations of α-hemolysin protein nanopores...
October 17, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/29045782/non-covalent-protein-arginine-deiminase-pad-inhibitors-are-efficacious-in-animal-models-of-multiple-sclerosis
#5
Elizabeth J Curiel Tejeda, Angelica M Bello, Ewa Wasilewski, Adam Koebel, Shannon Dunn, Lakshmi P Kotra
Peptidyl arginine deiminases have been shown to be hyperactive in neurodegenerative diseases including multiple sclerosis. An α-amino acid based core structure, derived from a hydantoin core, with unique heterocycles on the side chains, were synthesized as potential non-covalent inhibitors of PAD enzymes. Amongst the various heterocycles investigated, compound 23 carrying an imidazole moiety, exhibited the highest potency in this series with some selectivity for PAD2, and was further investigated in vivo. Pharmacokinetics in mice suggested the Cmax to be 12...
October 18, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29045531/phylogenetic-and-functional-signals-in-gymnosperm-ovular-secretions
#6
Massimo Nepi, Stefan Little, Massimo Guarnieri, Daniele Nocentini, Natalie Prior, Julia Gill, P Barry Tomlinson, Stefanie M Ickert-Bond, Cary Pirone, Ettore Pacini, Patrick von Aderkas
Background and Aims: Gymnosperms are either wind-pollinated (anemophilous) or both wind- and insect-pollinated (ambophilous). Regardless of pollination mode, ovular secretions play a key role in pollen capture, germination and growth; they are likely also involved in pollinator reward. Little is known about the broad-scale diversity of ovular secretions across gymnosperms, and how these may relate to various reproductive functions. This study analyses the sugar and amino acid profiles of ovular secretions across a range of ambophilous (cycads and Gnetales) and anemophilous gymnosperms (conifers) to place them in an evolutionary context of their possible functions during reproduction...
October 16, 2017: Annals of Botany
https://www.readbyqxmd.com/read/29045529/impact-of-genetic-variations-in-the-mapk-signaling-pathway-on-outcome-in-metastatic-colorectal-cancer-patients-treated-with-first-line-folfiri-and-bevacizumab-data-from-fire-3-and-tribe-trials
#7
M D Berger, S Stintzing, V Heinemann, D Yang, S Cao, Y Sunakawa, Y Ning, S Matsusaka, S Okazaki, Y Miyamoto, M Suenaga, M Schirripa, S Soni, W Zhang, A Falcone, F Loupakis, H-J Lenz
Background: The MAPK-interacting kinase 1 (MKNK1) is localized downstream of the RAS/RAF/ERK and the MAP3K1/MKK/p38 signaling pathway. Through phosphorylation MKNK1 regulates the function of eukaryotic translation initiation factor 4E, a key player in translational control, whose expression is often upregulated in metastatic colorectal cancer patients (mCRC). Preclinical data suggest that MKNK1 increases angiogenesis by upregulating angiogenic factors. We therefore hypothesize that variations in the MKNK1 gene predict outcome in mCRC patients treated with first-line FOLFIRI and bevacizumab (bev)...
August 2, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29045397/glucose-feeds-the-tca-cycle-via-circulating-lactate
#8
Sheng Hui, Jonathan M Ghergurovich, Raphael J Morscher, Cholsoon Jang, Xin Teng, Wenyun Lu, Lourdes A Esparza, Tannishtha Reya, Le Zhan, Jessie Yanxiang Guo, Eileen White, Joshua D Rabinowitz
Mammalian tissues are fuelled by circulating nutrients, including glucose, amino acids, and various intermediary metabolites. Under aerobic conditions, glucose is generally assumed to be burned fully by tissues via the tricarboxylic acid cycle (TCA cycle) to carbon dioxide. Alternatively, glucose can be catabolized anaerobically via glycolysis to lactate, which is itself also a potential nutrient for tissues and tumours. The quantitative relevance of circulating lactate or other metabolic intermediates as fuels remains unclear...
October 18, 2017: Nature
https://www.readbyqxmd.com/read/29045152/discovery-of-potent-and-orally-bioavailable-macrocyclic-peptide-peptoid-hybrid-cxcr7-modulators
#9
Markus Boehm, Kevin Beaumont, Rhys M Jones, Amit S Kalgutkar, Liying Zhang, Karen Atkinson, Guoyun Bai, Janice A Brown, Heather Eng, Gilles H Goetz, Brian R Holder, Bhagyashree Khunte, Sarah Lazzaro, Chris Limberakis, Sangwoo Ryu, Michael J Shapiro, Laurie Tylaska, Jiangli Yan, Rushia Turner, Siegfried S F Leung, Mahesh Ramaseshan, David A Price, Spiros Liras, Matthew P Jacobson, David J Earp, R Scott Lokey, Alan M Mathiowetz, Elnaz Menhaji-Klotz
The chemokine receptor CXCR7 is an attractive target for a variety of diseases. While several small molecule modulators of CXCR7 have been reported, peptidic macrocycles may provide advantages in terms of potency, selectivity, and reduced off-target activity. We produced a series of peptidic macrocycles that incorporate an N-linked peptoid functionality where the peptoid group enabled us to explore side chain diversity well beyond that of natural amino acids. At the same time, computational calculations and experimental assays were used to track and reduce polarity while closely monitoring physicochemical properties...
October 18, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29045069/association-of-natural-killer-cell-ligand-polymorphism-hla-c-asn80lys-with-the-development-of-anti-ssa-ro-associated-congenital-heart-block
#10
Hannah C Ainsworth, Miranda C Marion, Tiziana Bertero, Antonio Brucato, Rolando Cimaz, Nathalie Costedoat-Chalumeau, Micaela Fredi, Patrick Gaffney, Jennifer Kelly, Kateri Levesque, Alice Maltret, Nathalie Morel, Veronique Ramoni, Amelia Ruffatti, Carl D Langefeld, Jill P Buyon, Robert M Clancy
OBJECTIVE: Fetal exposure to maternal anti-SSA/Ro antibodies is necessary but not sufficient for the development of autoimmune congenital heart block (CHB), suggesting that other factors, such as fetal genetic predisposition, are important. Given the previously described association between major histocompatibility complex alleles and CHB risk, we undertook the present study to test the hypothesis that a variant form of HLA-C Asn80Lys, which binds with high affinity to an inhibitory killer cell immunoglobulin-like receptor (KIR) and thus renders natural killer (NK) cells incapable of restricting inflammation, contributes to the development of CHB...
October 17, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29045027/step-up-synthesis-of-periodic-mesoporous-organosilicas-with-the-framework-of-tyrosine-tyr-pmos-and-performance-on-horseradish-peroxidase-immobilization
#11
Jianqiang Wang, Wenqi Zhang, Changqing Gu, Wenpei Zhang, Man Zhou, Zhiwei Wang, Cheng Guo, Linbing Sun
A new amino-acid bridged periodic mesoporous organosilicas (PMOs) have been constructed via hydrolysis and condensation reactions under acid condition in the presence of template. The tyrosine bissilylated organic precursor (TBOS) was first prepared through multi-step reaction using tyrosine (natural amino acid) as starting material. The PMOs with the framework of tyrosine (Tyr-PMOs) were architected by simultaneously using TBOS and TEOS as complex silicon source in the condensation process. All the Tyr-PMOs materials were characterized by XRD, FT-IR, N2 adsorption-desorption, TEM, SEM and 29Si solid-state NMR to confirm the structure...
October 18, 2017: Chemistry, An Asian Journal
https://www.readbyqxmd.com/read/29045013/is-there-a-relationship-between-melanocytes-and-sensorineural-hearing-loss-clinical-evaluation-of-fifthy-one-alopecia-areata-patients
#12
Hasan Emre Koçak, Ayşe Şermin Filiz Acıpayam, Harun Acıpayam, Bilgen Çakıl Erdoğan, Nimet Yeşim Yıldız, Levent Küfeciler, Mustafa Suphi Elbistanlı, Kamil Hakan Kaya
Melanocytes are located in both the cochlea and vestibular organ of the inner ear. They are present in the hearing organ, in the intermediate layer of stria vascularis in the cochlea. The most important task of the stria vascularis is to provide the endolymph production necessary for normal hearing levels, especially high K(+) concentration, and to protect the positive endocochlear potential. Specifically, intermediate layer melanocytes express ionic channels, such as inwardly rectifying K+ channels and voltage-dependent outwardly rectifying K+...
October 17, 2017: Clinical Otolaryngology
https://www.readbyqxmd.com/read/29044998/liquid-chromatographic-resolution-of-proline-and-pipecolic-acid-derivatives-on-chiral-stationary-phases-based-on-18-crown-6-2-3-11-12-tetracarboxylic-acid
#13
Eun Sol Cho, Ji Yeong Sung, Jong Sung Jin, Myung Ho Hyun
Two liquid chromatographic chiral stationary phases based on (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid were applied to the resolution of the amide derivatives of cyclic α-amino acids including proline and pipecolic acid. Among the five amide derivatives of proline, aniline amide was resolved best on the first chiral stationary phase, which contains two N-H tethering amide groups, with the separation factor of 1.31 and the resolution of 2.60, and on the second chiral stationary phase, which contains two N-CH3 tethering amide groups, with the separation factor of 1...
October 17, 2017: Journal of Separation Science
https://www.readbyqxmd.com/read/29044994/characterization-and-expression-pattern-of-r-spondin1-in-cynoglossus-semilaevis
#14
Hailong Li, Wenteng Xu, Ying Zhu, Ning Zhang, Jialu Ma, Ai Sun, Zhongkai Cui, Fengtao Gao, Na Wang, Changwei Shao, Zhongdian Dong, Yangzhen Li
r-spondin1 (rspo1) encodes a secreted protein that is involved in the determination and differentiation of the mammalian ovary. However, little information is yet available for teleosts. Here, we identified a homologue of rspo1 in Cynoglossus semilaevis. The full-length cDNA of rspo1 had a length of 2,703 bp with an open reading frame of 834 bp, encoding a protein with a length of 277 amino-acids. rspo1 expression was detected via qRT-PCR in various tissues, and significant sexually dimorphic expression was observed in the gonads...
October 17, 2017: Journal of Experimental Zoology. Part B, Molecular and Developmental Evolution
https://www.readbyqxmd.com/read/29044950/biochemical-characterization-of-argininosuccinate-lyase-from-m-tuberculosis-significance-of-a-c-terminal-cysteine-in-catalysis-and-thermal-stability
#15
Archita Mishra, Avadhesha Surolia
Arginine biosynthesis pathway is crucial to the survival and pathogenesis of Mycobacterium tuberculosis (Mtb). Arginine is a critical amino acid that contributes to the inflection of cellular immune responses during pathogenesis. Argininosuccinate lyase from Mtb (MtArgH), the last enzyme in the pathway, catalyzes the production of arginine from argininosuccinic acid. MtArgH is an essential enzyme for the growth and survival of M. tuberculosis. We biochemically characterized MtArgH and deciphered the role of a previously unexplored cysteine (Cys(441) ) residue at the C-terminal region of the protein...
October 16, 2017: IUBMB Life
https://www.readbyqxmd.com/read/29044890/overexpression-of-serine-acetyltransferase-in-maize-leaves-increases-seed-specific-methionine-rich-zeins
#16
Xiaoli Xiang, Yongrui Wu, José Planta, Joachim Messing, Thomas Leustek
Maize kernels do not contain enough of the essential sulfur-amino acid methionine (Met) to serve as a complete diet for animals, even though maize has the genetic capacity to store Met in kernels. Prior studies indicated that the availability of the sulfur (S)-amino acids may limit their incorporation into seed storage proteins. Serine acetyltransferase (SAT) is a key control point for S-assimilation leading to Cys and Met biosynthesis and SAT overexpression is known to enhance S-assimilation without negative impact on plant growth...
October 16, 2017: Plant Biotechnology Journal
https://www.readbyqxmd.com/read/29044866/high-susceptibility-of-histidine-to-charge-solvation-revealed-by-cold-ion-spectroscopy
#17
Alexandr Y Pereverzev, Vladimir Kopysov, Oleg V Boyarkin
Histidine remained the last aromatic amino acid for which the intrinsic spectroscopic properties and structures were obscure. We measured the UV and IR spectra of protonated histidine, isolated in the gas phase, using photofragmentation cold ion spectroscopy. Unexpectedly, the UV absorption appears strongly redshifted relative to that of the cation in aqueous solutions. In investigating this phenomenon, we solved the geometries of all abundant conformers using IR conformer-selective spectroscopy and ab initio quantum chemical calculations...
October 18, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/29044752/zn-ii-interrupts-r4-r3-association-leading-to-accelerated-aggregation-of-tau-protein
#18
Vinesh Vijayan
Direct binding of divalent metal ion, especially Zn2+ have been shown to increase the rate of tau aggregation and enhance tau toxicity in cells. Hence understanding the molecular basis of the Zn2+ accelerated tau aggregation can potentially determine the molecular interactions modulating tau aggregation. Here we show that Zn2+ coordinate through the cysteine in R3 repeat and significantly accelerate the aggregation rate of the three repeat tau construct (K19) but the coordination is incapable of increasing the aggregation rate of the 20 amino acid peptide derived from the R3 repeat (R3) of tau...
October 17, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/29044608/nutrient-sensing-in-pancreatic-islets-lessons-from-congenital-hyperinsulinism-and-monogenic-diabetes
#19
REVIEW
Ming Lu, Changhong Li
Pancreatic beta cells sense changes in nutrients during the cycles of fasting and feeding and release insulin accordingly to maintain glucose homeostasis. Abnormal beta cell nutrient sensing resulting from gene mutations leads to hypoglycemia or diabetes. Glucokinase (GCK) plays a key role in beta cell glucose sensing. As one form of congenital hyperinsulinism (CHI), activating mutations of GCK result in a decreased threshold for glucose-stimulated insulin secretion and hypoglycemia. In contrast, inactivating mutations of GCK result in diabetes, including a mild form (MODY2) and a severe form (permanent neonatal diabetes mellitus (PNDM))...
October 16, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29044559/discovery-and-characterization-of-novel-trans-spliced-products-of-human-polyoma-jc-virus-late-transcripts-from-pml-patients
#20
A Sami Saribas, Julia DeVoto, Akhil Golla, Hassen S Wollebo, Martyn K White, Mahmut Safak
Although the human neurotropic polyomavirus, JC virus (JCV), was isolated almost a half century ago, understanding the molecular mechanisms governing its biology remains highly elusive. JCV infects oligodendrocytes and astrocytes in the central nervous system (CNS) and causes a fatal brain disease known as progressive multifocal leukoencephalopathy (PML) in immunocompromised individuals including AIDS. It has a small circular DNA genome (∼ 5 kb) and generates two primary transcripts from its early and late coding regions, producing several predicted alternatively spliced products mainly by cis-splicing...
October 16, 2017: Journal of Cellular Physiology
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