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Site directed mutations

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https://www.readbyqxmd.com/read/29777197/the-transition-state-structure-for-binding-between-taz1-of-cbp-and-the-disordered-hif-1%C3%AE-cad
#1
Ida Lindström, Eva Andersson, Jakob Dogan
Intrinsically disordered proteins (IDPs) are common in eukaryotes. However, relatively few experimental studies have addressed the nature of the rate-limiting transition state for the coupled binding and folding reactions involving IDPs. By using site-directed mutagenesis in combination with kinetics measurements we have here characterized the transition state for binding between the globular TAZ1 domain of CREB binding protein and the intrinsically disordered C-terminal activation domain of Hif-1α (Hif-1α CAD)...
May 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29775713/enhancement-of-catalytic-activity-and-thermostability-of-a-thermostable-cellobiohydrolase-from-chaetomium-thermophilum-by-site-directed-mutagenesis
#2
Chao Han, Weiguang Li, Chengyao Hua, Fengqing Sun, Pengsheng Bi, Qunqing Wang
Enzymatic saccharification of lignocellulosic biomass is increasingly applied in agricultural and industrial applications. Nevertheless, low performance in the extreme environment severely prevents the utilization of commercial enzyme preparations. To obtain cellobiohydrolases with improved catalytic activity and thermostability, structure-based rational design was performed based on a thermostable cellobiohydrolase CtCel6 from Chaetomium thermophilum. In the present study, four conserved and noncatalytic residue substitutions were generated via site-directed mutagenesis...
May 15, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29775643/myocardial-infarction-induced-hippocampal-microtubule-damage-by-cardiac-originating-microrna-1-in-mice
#3
Lin-Lin Sun, Ming-Jing Duan, Ji-Chao Ma, Ling Xu, Meng Mao, Das Biddyut, Qin Wang, Chao Yang, Shuai Zhang, Yi Xu, Lin Yang, You Tian, Ying Liu, Sheng-Nan Xia, Ke-Xin Li, Zhuo Jin, Qiaojie Xiong, Jing Ai
Cardiovascular diseases are risk factors for dementia, but the mechanisms remain elusive. Here, we report that myocardial infarction (MI) generated by the ligation of the left coronary artery (LCA) could lead to increased miR-1 levels in the hippocampus and blood with neuronal microtubule damage and decreased TPPP/p25 protein expression in the hippocampus. These changes could be prevented by a knockdown of miR-1 using hippocampal stereotaxic injections of anti-miR-1 oligonucleotide fragments carried by a lentivirus vector (lenti-pre-AMO-miR-1)...
May 15, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29774312/breast-cancer-prevention-current-approaches-and-future-directions
#4
REVIEW
Edward R Sauter
The topic of breast cancer prevention is very broad. All aspects of the topic, therefore, cannot be adequately covered in a single review. The objective of this review is to discuss strategies in current use to prevent breast cancer, as well as potential approaches that could be used in the future. This review does not discuss early detection strategies for breast cancer, including breast cancer screening. The breast is the most common site among women worldwide of noncutaneous cancer. Many clinical and genetic factors have been found to increase a woman's risk of developing the disease...
April 2018: European Journal of Breast Health
https://www.readbyqxmd.com/read/29772260/oxime-assisted-reactivation-of-tabun-inhibited-acetylcholinesterase-analysed-by-active-site-mutations
#5
Maja Katalinić, Goran Šinko, Nikolina Maček Hrvat, Tamara Zorbaz, Anita Bosak, Zrinka Kovarik
The antidotal property of oximes is attributed to their ability to reactivate acetylcholinesterase (AChE) inhibited by organophosphorus compounds (OP) such as pesticides and nerve warfare agents. Understanding their interactions within the active site of phosphylated AChE is of great significance for the search for more efficient reactivators, especially in the case of the most resistant OP to reactivation, tabun. Therefore, herein we studied the interactions and reactivation of tabun-inhibited AChE by site-directed mutagenesis and a series of bispyridinium oximes...
May 14, 2018: Toxicology
https://www.readbyqxmd.com/read/29766361/genetic-dissection-of-the-brca2-promoter-and-transcriptional-impact-of-dna-variants
#6
Eugenia Fraile-Bethencourt, Alberto Valenzuela-Palomo, Beatriz Díez-Gómez, Mar Infante, Mercedes Durán, Germán Marcos, Enrique Lastra, Susana Gómez-Barrero, Eladio A Velasco
PURPOSE: Promoter mutations may affect transcription and can be associated with human diseases. However, the promoters of the breast cancer (BC) genes are not regularly screened. Our goal was to investigate the BRCA2 promoter in order to study a possible correlation between impaired transcription and disease. METHODS: The proximal and core promoter of the BRCA2 gene was sequenced in 95 high-risk BC patients. A BRCA2-promoter insert [- 938 to + 312 from the transcription start site (TSS)] was generated and cloned into the firefly luciferase vector pGL4...
May 15, 2018: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/29762508/dicer1-syndrome-dicer1-mutations-in-rare-cancers
#7
REVIEW
Jake C Robertson, Cheryl L Jorcyk, Julia Thom Oxford
DICER1 syndrome is a rare genetic disorder that predisposes individuals to multiple cancer types. Through mutations of the gene encoding the endoribonuclease, Dicer, DICER1 syndrome disrupts the biogenesis and processing of miRNAs with subsequent disruption in control of gene expression. Since the first description of DICER1 syndrome, case reports have documented novel germline mutations of the DICER1 gene in patients with cancers as well as second site mutations that alter the function of the Dicer protein expressed...
May 15, 2018: Cancers
https://www.readbyqxmd.com/read/29762031/thermostability-improvement-of-the-d-allulose-3-epimerase-from-dorea-sp-cag-317-by-site-directed-mutagenesis-at-the-interface-regions
#8
Wenli Zhang, Yanmin Zhang, Jiawei Huang, Ziwei Chen, Tao Zhang, Cuie Guang, Wanmeng Mu
D-Allulose is a low-calorie sweetener and has broad applications in the food, cosmetics and pharmaceutical industries. Recently, most studies focuse on D-allulose production from D-fructose by D-allulose 3-epimerase (DAEase). However, the major blocker of industrial production of D-allulose is the poor thermostability. In this study, site-directed mutagenesis at the interface regions of Dorea sp. DAEase was carried out, and the F154Y/E191D/I193F mutation was obtained. The mutant protein displayed much higher thermostability, with a t1/2 value of 20...
May 15, 2018: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29761864/high-throughput-detection-and-screening-of-plantsmodified-by-geneediting-using-quantitative-real-time-pcr
#9
Cheng Peng, Hua Wang, Xiaoli Xu, Xiaofu Wang, Xiaoyun Chen, Wei Wei, Yongmin Lai, Guoquan Liu, Godwin Ian, Jieqin Li, Ling Zhang, Junfeng Xu
Gene editing techniques are becoming powerful tools for modifying target genes in organisms. Although several methods have been developed to detect gene-edited organisms, these techniques are time- and labour-intensive. Meanwhile, few studies have investigated high-throughput detection and screening strategies for plants modified by gene editing. In this study, we developed a simple, sensitive and high-throughput quantitative real-time(qPCR)-based method. The qPCR-based methodexploits two differently labelled probes that are placed within one amplicon at the gene editing target site to simultaneously detect the wild type and a gene-edited mutant...
May 15, 2018: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/29757631/understanding-which-residues-of-the-active-site-and-loop-structure-of-a-tyrosine-aminomutase-define-its-mutase-and-lyase-activities
#10
Gayanthi Attanayake, Tyler Walter, Kevin D Walker
Site-directed mutations and substrate analogs were used to gain insights into the branch-point reaction catalyzed by the 3,5-dihydro-5-methylidene-4H-imidazol-4-one (MIO)-tyrosine aminomutase from Oryza sativa ( OsTAM). Exchanging the active residues of ( OsTAM) (Y125C/N446K) for those in a phenylalanine aminomutase TcPAM altered its substrate specificity from tyrosine to phenylalanine. The aminomutase mechanism of ( OsTAM) surprisingly changed nearly exclusively to that of an ammonia lyase making cinnamic acid (>95%) over β-phenylalanine [Biochemistry 55, 3497-3503 (2016)]...
May 14, 2018: Biochemistry
https://www.readbyqxmd.com/read/29755477/glycan-shielding-and-modulation-of-hepatitis-c-virus-neutralizing-antibodies
#11
REVIEW
Muriel Lavie, Xavier Hanoulle, Jean Dubuisson
Hepatitis C virus (HCV) envelope glycoprotein heterodimer, E1E2, plays an essential role in virus entry and assembly. Furthermore, due to their exposure at the surface of the virion, these proteins are the major targets of anti-HCV neutralizing antibodies. Their ectodomain are heavily glycosylated with up to 5 sites on E1 and up to 11 sites on E2 modified by N-linked glycans. Thus, one-third of the molecular mass of E1E2 heterodimer corresponds to glycans. Despite the high sequence variability of E1 and E2, N-glycosylation sites of these proteins are generally conserved among the seven major HCV genotypes...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29755409/glial-cells-missing-1-regulates-equine-chorionic-gonadotrophin-beta-subunit-via-binding-to-the-proximal-promoter
#12
Jordan E Read, Victoria Cabrera-Sharp, Phoebe Kitscha, Judith E Cartwright, Peter J King, Robert C Fowkes, Amanda M de Mestre
Equine chorionic gonadotrophin (eCG) is a placental glycoprotein critical for early equine pregnancy and used therapeutically in a number of species to support reproductive activity. The factors in trophoblast that transcriptionally regulate eCGβ-subunit ( LHB ), the gene which confers the hormones specificity for the receptor, are not known. The aim of this study was to determine if glial cells missing 1 regulates LHB promoter activity. Here, studies of the LHB proximal promoter identified four binding sites for glial cells missing 1 (GCM1) and western blot analysis confirmed GCM1 was expressed in equine chorionic girdle (ChG) and surrounding tissues...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29754447/gain-of-function-mutations-in-beet-doda2-identify-key-residues-for-betalain-pigment-evolution
#13
Alexander Bean, Rasika Sunnadeniya, Neda Akhavan, Annabelle Campbell, Matthew Brown, Alan Lloyd
The key enzymatic step in betalain biosynthesis involves conversion of l-3,4-dihydroxyphenylalanine (l-DOPA) to betalamic acid. One class of enzymes capable of this is 3,4-dihydroxyphenylalanine 4,5-dioxygenase (DODA). In betalain-producing species, multiple paralogs of this gene are maintained. This study demonstrates which paralogs function in the betalain pathway and determines the residue changes required to evolve a betalain-nonfunctional DODA into a betalain-functional DODA. Functionalities of two pairs of DODAs were tested by expression in beets, Arabidopsis and yeast, and gene silencing was performed by virus-induced gene silencing...
May 13, 2018: New Phytologist
https://www.readbyqxmd.com/read/29754184/discovery-of-a-potent-and-mutant-selective-egfr-inhibitor-that-overcomes-t790m-mediated-resistance-in-lung-cancer
#14
Dong Ha Kim, Yun Jung Choi, Seon Ye Kim, Jung-Eun Lee, Ki Jung Sung, Young Hoon Sung, Woo Sung Kim, Sung-Eun Kim, Hyung Chul Ryu, Jae Sun Kim, Lu Guangying, Chang-Min Choi, Jin Kyung Rho, Jae Cheol Lee
BACKGROUND: Despite remarkable activity in epidermal growth factor receptor (EGFR)-mutant lung cancer patients, the clinical efficacy of EGFR tyrosine kinase inhibitors (TKIs) is limited by the emergence of acquired resistance, which is mostly caused by a secondary T790M mutation. Fortunately, newly developed, mutant-selective EGFR-TKIs against T790M have been proven as an effective therapeutic approach although only osimertinib has received the FDA approval until now. OBJECTIVE: To determine the in vitro and in vivo efficacy of a new EGFR TKI, OBX1-012 in cells with mutant EGFR...
May 12, 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29753890/characterization-of-the-promoter-of-white-spot-syndrome-virus-immediate-early-gene-wsv249
#15
Zi Yang, Xiaomin Xu, Fang Li, Feng Yang
White spot syndrome virus immediate early (IE) gene wsv249 encodes an E3 ubiquitin ligase that can interact with a shrimp ubiquitin-conjugating enzyme to mediate ubiquitination. In this study, to understand the transcriptional regulation of wsv249, a serial of 5'-truncated mutations were made on its promoter and the activities of mutated promoters was analyzed. Four 25 bp regions potentially containing either positive or negative regulatory elements were identified. Notably, the deletion of -275/-250, which abolished a cAMP-response element (CRE), greatly reduced the promoter activity by 84...
May 10, 2018: Virus Research
https://www.readbyqxmd.com/read/29752942/structure-based-protein-engineering-of-bacterial-%C3%AE-xylosidase-to-increase-the-production-yield-of-xylobiose-from-xylose
#16
Seokho Hong, Myungok Kyung, Inseong Jo, Yong-Ro Kim, Nam-Chul Ha
Xylobiose consists of two molecules of xylose and has been highly recognized as a food supplement because it possesses high prebiotic functions. β-xylosidase exhibits enzymatic activity to hydrolyze xylobiose, and the enzyme can also catalyze the reverse reaction in the presence of high concentrations of xylose. Previously, β-xylosidase from Bacillus pumilus IPO (BpXynB), belonging to GH family 43, was employed to produce xylobiose from xylose. To improve the enzymatic efficiency, this study determined the high-resolution structure of BpXynB in a complex with xylobiose and engineered BpXynB based on the structures...
May 9, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29752939/structural-and-biochemical-characterization-of-the-yeast-hd-domain-containing-protein-ygk1-reveals-a-metal-dependent-nucleoside-5-monophosphatase
#17
Jingsi Yang, Fei Wang, Dan Yang, Ke Zhou, Min Liu, Zengqiang Gao, Peng Liu, Yuhui Dong, Jianjun Zhang, Quansheng Liu
HD-domain is a conserved domain, with the signature of histidine and aspartic (HD) residues doublets. HD-domain proteins may possess nucleotidase and phosphodiesterase activities, and they play important roles in signaling and nucleotide metabolism. In yeast, HD-domain proteins with nucleotidase activity remained unexplored. Here, we biochemically and structurally characterized two HD domain proteins YGK1 (YGL101W) and YB92 (YBR242W) from Saccharomyces cerevisiae as nucleoside 5'-monophosphatases, with substrate preference for deoxyribonucleoside 5'-monophosphatase over ribonucleoside 5'-monophosphatase...
May 9, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29752755/jasmonic-acid-ethylene-signaling-coordinates-hydroxycinnamic-acid-amides-biosynthesis-through-ora59-transcription-factor
#18
Jinbo Li, Kaixuan Zhang, Yu Meng, Jianping Hu, Mengqi Ding, Jiahui Bian, Mingli Yan, Jianming Han, Meiliang Zhou
Hydroxycinnamic acid amides (HCAAs) are a class of antimicrobial metabolites involved in plant defense against necrotrophic pathogens, including Alternaria brassicicola and Botrytis cinerea. The agmatine coumaroyl transferase (AtACT) is the key enzyme to catalyze the last reaction in the biosynthesis of HCAAs, including p-coumaroylagmatine (CouAgm) and feruloylagmatine in Arabidopsis thaliana. However, it is currently unknown about the regulatory mechanism of the AtACT gene expression. Yeast one-hybrid screening using the AtACT promoter as bait isolated the key positive regulator ORA59 that is involved in jasmonic acid/ethylene (JA/ET) mediated plant defense responses...
May 11, 2018: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/29752607/farseer-nmr-automatic-treatment-analysis-and-plotting-of-large-multi-variable-nmr-data
#19
João M C Teixeira, Simon P Skinner, Miguel Arbesú, Alexander L Breeze, Miquel Pons
We present Farseer-NMR ( https://git.io/vAueU ), a software package to treat, evaluate and combine NMR spectroscopic data from sets of protein-derived peaklists covering a range of experimental conditions. The combined advances in NMR and molecular biology enable the study of complex biomolecular systems such as flexible proteins or large multibody complexes, which display a strong and functionally relevant response to their environmental conditions, e.g. the presence of ligands, site-directed mutations, post translational modifications, molecular crowders or the chemical composition of the solution...
May 11, 2018: Journal of Biomolecular NMR
https://www.readbyqxmd.com/read/29752549/promising-new-agents-for-colorectal-cancer
#20
REVIEW
Satya Das, Kristen K Ciombor, Sigurdis Haraldsdottir, Richard M Goldberg
Choosing the optimal treatment approach for patients with metastatic colorectal cancer (mCRC) demands that oncologists assess both clinical and genomic variables and individualize care based upon the findings. Clinically, choices depend on assessing the side of the colon in which the primary tumor originates, the sites and burden of metastatic disease, the patient's performance status, and their individual comorbidities. Genomic assessment of the tumor to discern the mutational status of genes such as RAS/RAF, HER2, and TRK, as well as assessing whether tumors have defective mismatch repair (dMMR) or high microsatellite instability (MSI-H), all factor in to potential treatment options and can determine clinical trial eligibility...
May 11, 2018: Current Treatment Options in Oncology
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