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https://www.readbyqxmd.com/read/29243092/-multiple-partial-recognitions-in-dynamic-equilibrium-in-the-binding-sites-of-proteins-form-the-molecular-basis-of-promiscuous-recognition-of-structurally-diverse-ligands
#1
REVIEW
Daisuke Kohda
Promiscuous recognition of ligands by proteins is as important as strict recognition in numerous biological processes. In living cells, many short, linear amino acid motifs function as targeting signals in proteins to specify the final destination of the protein transport. In general, the target signal is defined by a consensus sequence containing wild-characters, and hence represented by diverse amino acid sequences. The classical lock-and-key or induced-fit/conformational selection mechanism may not cover all aspects of the promiscuous recognition...
December 14, 2017: Biophysical Reviews
https://www.readbyqxmd.com/read/29242966/cyp1a1-genetic-polymorphism-is-a-promising-predictor-to-improve-chemotherapy-effects-in-patients-with-metastatic-breast-cancer-treated-with-docetaxel-plus-thiotepa-vs-docetaxel-plus-capecitabine
#2
Xinna Zhou, Guoliang Qiao, Xiaoli Wang, Qingkun Song, Michael A Morse, Amy Hobeika, William R Gwin, Jun Ren, H Kim Lyerly
PURPOSE: A prospective study was performed to compare the outcome for metastatic breast cancer (MBC) patients treated with docetaxel plus thiotepa (DT) or docetaxel plus capecitabine (DC), and to explore the value of CYP1A1*2C polymorphisms in predicting clinical efficacy of these chemotherapies. METHODS: MBC patients (n = 130) were randomized to treatment with DT (n = 65) or DC (n = 65). Response rate, disease control rate, progression-free and overall survival were monitored...
December 14, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29242061/phosphorylation-of-ser-525-in-%C3%AE-pix-impairs-nox1-activating-ability-in-caco-2%C3%A2-cells
#3
Yuuki Kaito, Ryosuke Kataoka, Tatsuya Mihara, Kento Takechi, Akira Takahira, Shuhei Watanabe, Fei Han, Minoru Tamura
βPix activates Nox1, an O2--generating NADPH oxidase, through Rac activation. In this study, we found that S525E mutation of βPix eliminated its Nox1-activating ability in transfected Caco-2 cells. Unexpectedly, affinity for Rac was not diminished but rather enhanced by S525E mutation, and guanine nucleotide exchange factor (GEF) activity was not altered. The N-terminal fragment (amino acids 1-400) showed similar Rac-binding and GEF activity to wild-type βPix. In contrast, the C-terminal fragment (amino acids 408-646) had higher Rac-binding activity, particularly for Rac-GTP, than wild-type βPix, and showed no GEF activity...
December 11, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29241000/possible-existence-of-%C3%AE-sheets-in-the-amyloid-fibrils-formed-by-a-ttr105-115-mutant
#4
Mary Rose Hilaire, Bei Ding, Debopreeti Mukherjee, Jianxin Chen, Feng Gai
Herein, we combine several methods to characterize the fibrils formed by a TTR105-115 mutant in which Leu111 is replaced by the unnatural amino acid aspartic acid 4-methyl ester. We find that this mutant peptide exhibits significantly different aggregation behavior than the wild-type peptide: (1) it forms fibrils with a much faster rate, (2) its fibrils lack the long-range helical twists observed in TTR105-115 fibrils, (3) its fibrils exhibit a giant far-UV circular dichroism signal, and (4) its fibrils give rise to an unusual amide I' band consisting of four distinct and sharp peaks...
December 14, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29237719/ift20-modulates-ciliary-pdgfr%C3%AE-signaling-by-regulating-the-stability-of-cbl-e3-ubiquitin-ligases
#5
Fabian Marc Schmid, Kenneth Bødtker Schou, Martin Juel Vilhelm, Maria Schrøder Holm, Loretta Breslin, Pietro Farinelli, Lars Allan Larsen, Jens Skorstengaard Andersen, Lotte Bang Pedersen, Søren Tvorup Christensen
Primary cilia have pivotal roles as organizers of many different signaling pathways, including platelet-derived growth factor receptor α (PDGFRα) signaling, which, when aberrantly regulated, is associated with developmental disorders, tumorigenesis, and cancer. PDGFRα is up-regulated during ciliogenesis, and ciliary localization of the receptor is required for its appropriate ligand-mediated activation by PDGF-AA. However, the mechanisms regulating sorting of PDGFRα and feedback inhibition of PDGFRα signaling at the cilium are unknown...
December 13, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/29237113/the-replication-protein-cdc6-suppresses-centrosome-over-duplication-in-a-manner-independent-of-its-atpase-activity
#6
Gwang Su Kim, Inyoung Lee, Ji Hun Kim, Deog Su Hwang
The Cdc6 protein is essential for the initiation of chromosomal replication and functions as a licensing factor to maintain chromosome integrity. During the S and G2 phases of the cell cycle, Cdc6 has been found to inhibit the recruitment of pericentriolar material (PCM) proteins to the centrosome and to suppress centrosome over-duplication. In this report, we analyzed the correlation between these two functions of Cdc6 at the centrosome. Cdc6 depletion increased the population of cells showing centrosome over-duplication and premature centrosome separation; Cdc6 expression reversed these changes...
December 12, 2017: Molecules and Cells
https://www.readbyqxmd.com/read/29236215/phylogenetic-comparison-of-the-vp7-vp4-vp6-and-nsp4-genes-of-rotaviruses-isolated-from-children-in-nizhny-novgorod-russia-2015-2016-with-cogent-genes-of-the-rotarix-and-rotateq-vaccine-strains
#7
O V Morozova, T A Sashina, N V Epifanova, V V Zverev, A U Kashnikov, N A Novikova
Group A rotaviruses (RVA) are one of the leading causes of gastroenteritis in young children worldwide. The introduction of universal mass vaccination around the world has contributed to a reduction in hospitalizations and outpatient visits associated with rotavirus infection. Continued surveillance of RVA strains is needed to determine long-term effects of vaccine introduction. In the present work, we carried out the analysis of the genotypic diversity of RVA strains isolated in Nizhny Novgorod (Russia) during the 2015-2016 epidemic season...
December 13, 2017: Virus Genes
https://www.readbyqxmd.com/read/29234041/evolution-of-a-flipped-pathway-creates-metabolic-innovation-in-tomato-trichomes-through-bahd-enzyme-promiscuity
#8
Pengxiang Fan, Abigail M Miller, Xiaoxiao Liu, A Daniel Jones, Robert L Last
Plants produce hundreds of thousands of structurally diverse specialized metabolites via multistep biosynthetic networks, including compounds of ecological and therapeutic importance. These pathways are restricted to specific plant groups, and are excellent systems for understanding metabolic evolution. Tomato and other plants in the nightshade family synthesize protective acylated sugars in the tip cells of glandular trichomes on stems and leaves. We describe a metabolic innovation in wild tomato species that contributes to acylsucrose structural diversity...
December 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/29233696/molecular-cloning-and-characterization-of-the-glutathione-reductase-gene-from-stipa-purpurea
#9
Qiuli Wang, Yanan Pu, Danni Yang, Xin Yin, Zhaorong He, Yunqiang Yang, Yongping Yang
Reactive oxygen species (ROS) are a key factor in abiotic stresses; excess ROS is harmful to plants. Glutathione reductase (GR) plays an important role in scavenging ROS in plants. Here, a GR gene, named SpGR, was cloned from Stipa purpurea and characterized. The full-length open reading frame was 1497 bp, encoding 498 amino acids. Subcellular localization analysis indicated that SpGR was localized to both the plasma membrane and nucleus. The expression of SpGR was induced by cold, salt, and drought stresses...
December 9, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29230615/association-of-604g-a-and-501a-c-ghrelin-and-obestatin-prepropeptide-gene-polymorphisms-with-polycystic-ovary-syndrome
#10
Talaat Dabbaghi Ghaleh, Somayeh Saadat Skandari, Reza Najafipour, Zahra Rashvand, Masoud Darabi, Mehdi Sahmani
Ghrelin hormone has an important role in a wide range of metabolic and non-metabolic processes. Polymorphisms of ghrelin gene could be associated with a large number of diseases. The aim of this study was to evaluate the association of -604G/A and -501A/C polymorphisms in ghrelin and obestatin prepropeptide gene (GHRL) with polycystic ovary syndrome (PCOS) in a sample of Iranian women. One hundred and fifty-two women with PCOS and 162 age-matched apparently healthy women as control group were enrolled in this study...
December 11, 2017: Biochemical Genetics
https://www.readbyqxmd.com/read/29230603/amp-activated-protein-kinase-activation-in-mediating-phenylalanine-induced-neurotoxicity-in-experimental-models-of-phenylketonuria
#11
Lihua Lu, Xiaoming Ben, Lingling Xiao, Min Peng, Yongjun Zhang
Phenylketonuria (PKU), one of the most prevalent autosomal recessive disorders of amino acid metabolism, is characterized by abnormal accumulation of phenylalanine, which can lead to intellectual disability. The main pathologic changes in the central nervous system of untreated phenylketonuric patients are reductions in the number of axons, dendrites, and synapses in the brain. Such alterations are thought to be mainly associated with the toxic effects caused by phenylalanine. However, the underlying molecular mechanisms have not been fully elucidated...
December 11, 2017: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/29229304/functional-characterization-of-the-g162r-and-d216h-genetic-variants-of-human-cyp17a1
#12
C P Capper, J Liu, L R McIntosh, J M Larios, M D Johnson, P F Hollenberg, Y Osawa, R J Auchus, J M Rae
Cytochrome P450 17A1 (CYP17A1) is a dual-function enzyme catalyzing reactions necessary for cortisol and androgen biosynthesis. CYP17A1 is a validated drug target for prostate cancer as CYP17A1 inhibition significantly reduces circulating androgens and improves survival in castration-resistant prostate cancer. Germline CYP17A1 genetic variants with altered CYP17A1 activity manifesting as various endocrinopathies are extremely rare; however, characterizing these variants provides critical insights into CYP17A1 protein structure and function...
December 8, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/29226127/the-kinase-stk3-interacts-with-the-viral-structural-protein-vp1-and-inhibits-foot-and-mouth-disease-virus-replication
#13
Huisheng Liu, Qiao Xue, Qiaoying Zeng, Zixiang Zhu, Haixue Zheng
Foot-and-mouth disease virus (FMDV) is the etiological agent of FMD, which affects domestic and wild cloven-hoofed animals. The structural protein VP1 plays an important role in FMDV pathogenesis. However, the interacting partners of VP1 in host cells and the effects of these interactions in FMDV replication remain incompletely elucidated. Here, we identified a porcine cell protein, serine/threonine kinase 3 (STK3), which interacts with FMDV VP1 using the yeast two-hybrid system. The VP1-STK3 interaction was further confirmed by coimmunoprecipitation experiments in human embryonic kidney 293T and porcine kidney 15 (PK-15) cells...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29224332/statistical-coupling-analysis-guided-library-design-for-discovery-of-mutant-luciferases
#14
Mira D Liu, Elliot A Warner, Charlotte E Morrissey, Caitlyn W Fick, Taia S Wu, Marya Y Ornelas, Gabriela V Ochoa, Brendan Zhang, Colin M Rathbun, William B Porterfield, Jennifer A Prescher, Aaron Morgan Leconte
Directed evolution has proven to be an invaluable tool for protein engineering; however, there is still a need for developing new approaches to continue to improve the efficiency and efficacy of these methods. Here, we demonstrate a new method for library design that applies a previously developed bioinformatic method, Statistical Coupling Analysis (SCA). SCA uses homologous enzymes to identify amino acid positions that are mutable, functionally important, and engage in synergistic interactions between amino acids...
December 11, 2017: Biochemistry
https://www.readbyqxmd.com/read/29223463/terfenadine-metabolism-of-human-cytochrome-p450-2j2-containing-genetic-variations-g312r-p351l-and-p115l
#15
Dabin Jeong, Hyoung-Goo Park, Young-Ran Lim, Yejin Lee, Vitchan Kim, Myung-A Cho, Donghak Kim
The human cytochrome P450 2J2 is involved in several metabolic reactions, including the oxidation of important therapeutics and epoxidation of endogenous arachidonic acid. At least ten genetic variations of P450 2J2 have been identified, but their effects on enzymatic activity have not been clearly characterized. Here, we evaluated the functional effects of three genetic variations of P450 2J2 (G312R, P351L, and P115L). Recombinant enzymes of wild-type and three variant P450 2J2 were heterologously expressed in Escherichia coli and purified...
November 11, 2017: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/29223330/expression-of-a-populus-histone-deacetylase-gene-84khda903-in-tobacco-enhances-drought-tolerance
#16
Xujun Ma, Bing Zhang, Chunjuan Liu, Botong Tong, Tao Guan, Dean Xia
Histone deacetylases (HDACs) play a key role in regulating plant growth, development and stress responses. However, functions of HDACs in woody plants are largely unknown. In this study, a novel gene encoding a RPD3/HDA1-type histone deacetylase was cloned from 84K poplar (Populus alba×Populus glandulosa) and designated as 84KHDA903. The 84KHDA903 encodes a protein composed of 500 amino acid residues, which contains a conserved HDAC domain. Transient expression of 84KHDA903 in onion epidermal cells suggested that it was exclusively localized in nucleus...
December 2017: Plant Science: An International Journal of Experimental Plant Biology
https://www.readbyqxmd.com/read/29220360/substitutions-of-prp-n-terminal-histidine-residues-modulate-scrapie-disease-pathogenesis-and-incubation-time-in-transgenic-mice
#17
Sabina Eigenbrod, Petra Frick, Uwe Bertsch, Gerda Mitteregger-Kretzschmar, Janina Mielke, Marko Maringer, Niklas Piening, Alexander Hepp, Nathalie Daude, Otto Windl, Johannes Levin, Armin Giese, Vignesh Sakthivelu, Jörg Tatzelt, Hans Kretzschmar, David Westaway
Prion diseases have been linked to impaired copper homeostasis and copper induced-oxidative damage to the brain. Divalent metal ions, such as Cu2+ and Zn2+, bind to cellular prion protein (PrPC) at octapeptide repeat (OR) and non-OR sites within the N-terminal half of the protein but information on the impact of such binding on conversion to the misfolded isoform often derives from studies using either OR and non-OR peptides or bacterially-expressed recombinant PrP. Here we created new transgenic mouse lines expressing PrP with disrupted copper binding sites within all four histidine-containing OR's (sites 1-4, H60G, H68G, H76G, H84G, "TetraH>G" allele) or at site 5 (composed of residues His-95 and His-110; "H95G" allele) and monitored the formation of misfolded PrP in vivo...
2017: PloS One
https://www.readbyqxmd.com/read/29218438/two-novel-bocaparvovirus-species-identified-in-wild-himalayan-marmots
#18
Yuanyun Ao, Xiaoyue Li, Lili Li, Xiaolu Xie, Dong Jin, Jiemei Yu, Shan Lu, Zhaojun Duan
Bocaparvovirus (BOV) is a genetically diverse group of DNA viruses and a possible cause of respiratory, enteric, and neurological diseases in humans and animals. Here, two highly divergent BOVs (tentatively named as Himalayan marmot BOV, HMBOV1 and HMBOV2) were identified in the livers and feces of wild Himalayan marmots in China, by viral metagenomic analysis. Five of 300 liver samples from Himalayan marmots were positive for HMBOV1 and five of 99 fecal samples from these animals for HMBOV2. Their nearly complete genome sequences are 4,672 and 4,887 nucleotides long, respectively, with a standard genomic organization and containing protein-coding motifs typical for BOVs...
December 5, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/29218040/adaptation-of-lactobacillus-casei-zhang-to-gentamycin-involves-an-alkaline-shock-protein
#19
Wenyi Zhang, Huiling Guo, Chenxia Cao, Lina Li, Lai-Yu Kwok, Heping Zhang, Zhihong Sun
Lactobacillus (L. casei) Zhang is a koumiss-originated probiotic strain, which was used as a model in a long-term antibiotics-driven evolution experiment to reveal bacterial evolutionary dynamics; and we isolated gentamycin-resistant L. casei Zhang descendents. To decipher the gentamycin resistance mechanism, here we cultivated the parental L. casei Zhang and its descendent cells in an antibiotics-containing environment to compare their global protein expression profiles using the iTRAQ-based proteomic approach...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29216588/nmr-study-of-mutations-of-glycine-52-of-the-catalytic-domain-of-diphtheria-toxin
#20
Simon Sauvé, Geneviève Gingras, Yves Aubin
Cross-reacting-material 197 (CRM197) is a naturally occurring non-toxic mutant of diphtheria toxin (DT) that is one of the few carrier protein used in the manufacture of polysaccharide vaccines targeting bacterial pathogens such as Neisseria meningitidis, Streptococcus pneumaniae and Haemophilus influenzae. A detailed explanation in structural terms for the lack of toxicity has started to emerge with the report of the X-ray structure of CRM197. Here, we present an NMR spectroscopy study of the wild-type catalytic domain of diphtheria toxin and the effects of mutations at residue 52 on its conformation...
December 2, 2017: Journal of Pharmaceutical and Biomedical Analysis
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