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Enzymology

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https://www.readbyqxmd.com/read/27894770/activity-based-targeting-of-secretory-phospholipase-a2-enzymes-a-fatty-acid-binding-protein-assisted-approach
#1
Amir Keshavarz, Ligia Zelaya, Jasmeet Singh, Radha Ranganathan, Joseph Hajdu
Syntheses and enzymological characterization of fluorogenic substrate probes targeting secretory phospholipase A2 (sPLA2) for detection and quantitative assays are presented. Three fluorogenic phosphatidylcholine analogs PC-1, PC-2, and PC-3 each containing the duo of 7-mercapto-4-methyl-coumarin fluorophore and 2,4-dinitroanaline quencher on either tail were synthesized from (R)-3-amino-1,2-propanediol and R-(-)-2,2-dimethyl-1,3-dioxolane-4-methanol. These small reporter groups are advantageous in preserving natural membrane integrity...
November 25, 2016: Chemistry and Physics of Lipids
https://www.readbyqxmd.com/read/27865713/platensimycin-and-platencin-inspirations-for-chemistry-biology-enzymology-and-medicine
#2
REVIEW
Jeffrey D Rudolf, Liao-Bin Dong, Ben Shen
Natural products have served as the main source of drugs and drug leads, and natural products produced by microorganisms are one of the most prevalent sources of clinical antibiotics. Their unparalleled structural and chemical diversities provide a basis to investigate fundamental biological processes while providing access to a tremendous amount of chemical space. There is a pressing need for novel antibiotics with new mode of actions to combat the growing challenge of multidrug resistant pathogens. This review begins with the pioneering discovery and biological activities of platensimycin (PTM) and platencin (PTN), two antibacterial natural products isolated from Streptomyces platensis...
November 16, 2016: Biochemical Pharmacology
https://www.readbyqxmd.com/read/27826836/enzymology-of-mammalian-dna-methyltransferases
#3
Renata Z Jurkowska, Albert Jeltsch
DNA methylation is currently one of the hottest topics in basic and biomedical research. Despite tremendous progress in understanding the structures and biochemical properties of the mammalian DNA nucleotide methyltransferases (DNMTs), principles of their regulation in cells have only begun to be uncovered. In mammals, DNA methylation is introduced by the DNMT1, DNMT3A, and DNMT3B enzymes, which are all large multi-domain proteins. These enzymes contain a catalytic C-terminal domain with a characteristic cytosine-C5 methyltransferase fold and an N-terminal part with different domains that interacts with other proteins and chromatin and is involved in targeting and regulation of the DNMTs...
2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27821711/low-potential-of-basimglurant-to-be-involved-in-drug-drug-interactions-influence-of-non-michaelis-menten-cyp-kinetics-on-fraction-metabolized
#4
Stephen M Fowler, Elena Guerini, NaHong Qiu, Yumi Cleary, Neil J Parrott, Gerard Greig, Navita L Mallalieu
Basimglurant, a novel mGlu5 negative allosteric modulator under development for the treatment of major depressive disorder, is cleared via cytochrome P450 (CYP) mediated oxidative metabolism. Initial enzyme phenotyping studies indicated that CYP3A4/5 dominated basimglurant metabolism and highlighted a risk for drug-drug interactions when comedicated with strong CYP3A4/5 inhibitors or inactivators. However, a clinical drug-drug interaction (DDI) study using the potent and selective CYP3A4/5 inhibitor ketoconazole resulted in an AUCi/AUC ratio of only 1...
November 7, 2016: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/27793290/a-multicolor-single-molecule-fret-approach-to-study-protein-dynamics-and-interactions-simultaneously
#5
M Götz, P Wortmann, S Schmid, T Hugel
Single-molecule Förster resonance energy transfer (smFRET) is a versatile tool for studying biomolecules in a quantitative manner. Multiple conformations within and interactions between biomolecules can be detected and their kinetics can be determined. Thus, smFRET has become an essential tool in enzymology. Ordinary two-color smFRET experiments can provide only limited insight into the function of biological systems, which commonly consist of more than two components. A complete understanding of complex multicomponent biological systems requires correlated information on conformational rearrangements on the one hand and transient interactions with binding partners on the other...
2016: Methods in Enzymology
https://www.readbyqxmd.com/read/27788133/of-rings-and-rods-regulating-cohesin-entrapment-of-dna-to-generate-intra-and-intermolecular-tethers
#6
REVIEW
Robert V Skibbens
The clinical relevance of cohesin in DNA repair, tumorigenesis, and severe birth defects continues to fuel efforts in understanding cohesin structure, regulation, and enzymology. Early models depicting huge cohesin rings that entrap two DNA segments within a single lumen are fading into obscurity based on contradictory findings, but elucidating cohesin structure amid a myriad of functions remains challenging. Due in large part to integrated uses of a wide range of methodologies, recent advances are beginning to cast light into the depths that previously cloaked cohesin structure...
October 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27784173/high-performance-enzyme-kinetics-of-turnover-activation-and-inhibition-for-translational-drug-discovery
#7
Rumin Zhang, Kenny Wong
Enzymes are the macromolecular catalysts of many living processes and represent a sizable proportion of all druggable biological targets. Enzymology has been practiced just over a century during which much progress has been made in both the identification of new enzymes and the development of novel methodologies for enzyme kinetics. Areas covered: This review aims to address several key practical aspects in enzyme kinetics in reference to translational drug discovery research. The authors first define what constitutes a high performance enzyme kinetic assay...
October 27, 2016: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/27770859/usefulness-of-alginate-lyases-derived-from-marine-organisms-for-the-preparation-of-alginate-oligomers-with-various-bioactivities
#8
S Takeshita, T Oda
Alginate-degrading enzyme, alginate lyase, catalyzes the cleavage of glycosidic 1-4 O-linkages between uronic acid residues of alginate by a β-elimination reaction leaving a 4-deoxy-l-erythro-hex-4-ene pyranosyluronate as nonreducing terminal end. The enzymes from a wide variety of sources such as marine molluscs, seaweeds, and marine bacteria have been discovered and studied not only from a point of view of enzymological interest of enzyme itself but also for elucidation of fine chemical structure of alginate, structure-activity relationship of alginate, and biological activities and physicochemical features of the enzymatic digestion products...
2016: Advances in Food and Nutrition Research
https://www.readbyqxmd.com/read/27770411/micellar-enzymology-for-thermal-ph-and-solvent-stability
#9
Shelley D Minteer
This chapter describes methods for enzyme stabilization using micellar solutions. Micellar solutions have been shown to increase the thermal stability, as well as the pH and solvent tolerance of enzymes. This field is traditionally referred to as micellar enzymology. This chapter details the use of ionic and nonionic micelles for the stabilization of polyphenol oxidase, lipase, and catalase, although this method could be used with any enzymatic system or enzyme cascade system.
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27768865/cutting-choline-with-radical-scissors
#10
Joan B Broderick, James D Moody
The human gut microbiome is the source of not only microbial diversity, but also of interesting chemical reactions and enzymology. An excellent example of this is CutC, an enzyme that makes trimethylamine (TMA). In this issue of Cell Chemical Biology, Bodea et al. (2016) show how CutC uses a glycyl radical to perform C-N bond cleavage needed for TMA production.
October 20, 2016: Cell Chemical Biology
https://www.readbyqxmd.com/read/27767076/direct-and-indirect-mechanisms-of-klk4-inhibition-revealed-by-structure-and-dynamics
#11
Blake T Riley, Olga Ilyichova, Mauricio G S Costa, Benjamin T Porebski, Simon J de Veer, Joakim E Swedberg, Itamar Kass, Jonathan M Harris, David E Hoke, Ashley M Buckle
The kallikrein-related peptidase (KLK) family of proteases is involved in many aspects of human health and disease. One member of this family, KLK4, has been implicated in cancer development and metastasis. Understanding mechanisms of inactivation are critical to developing selective KLK4 inhibitors. We have determined the X-ray crystal structures of KLK4 in complex with both sunflower trypsin inhibitor-1 (SFTI-1) and a rationally designed SFTI-1 derivative to atomic (~1 Å) resolution, as well as with bound nickel...
October 21, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27744484/beta-cyanoalanine-synthase-pathway-as-a-homeostatic-mechanism-for-cyanide-detoxification-as-well-as-growth-and-development-in-higher-plants
#12
Hafiz Mamoon Rehman, Zahid Hussain Shah, Muhammad Amjad Nawaz, Muhammad Qadir Ahmad, Seung Hwan Yang, Kang Hee Kho, Gyuhwa Chung
This review provides an insight into the beta-cyanoalanine synthase pathway in higher plants for cyanide (CN) detoxification and describes how it contributes to various physiological activities, such as plant growth and development. In higher plants, CN is produced as a natural toxin through the biosynthesis of ethylene and camalexin, the degradation of glucosinolates and cyanogenic glycosides, the oxidation of amino acids, and the metabolism of glyoxylate and hydroxylamine. To maintain cellular homeostasis by maintaining CN at non-toxic levels, plants have evolved four different biochemical pathways: the β-cyanoalanine synthase pathway (beta-CASP), the thiocyanate pathway, the formamide hydrolase pathway, and the natural release of CN through volatilization...
October 15, 2016: Planta
https://www.readbyqxmd.com/read/27718484/progress-and-impact-of-enzyme-measurement-standardization
#13
Ilenia Infusino, Erika Frusciante, Federica Braga, Mauro Panteghini
International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) has established reference measurement procedures (RMPs) for the most popular enzymes. Manufacturers should assign values to commercial calibrators traceable to these RMPs to achieve equivalent results in clinical samples, independent of reagent kits, instruments, and laboratory where the measurement is carried out. The situation is, however, far from acceptable. Some manufacturers continue to market assays giving results that are not traceable to internationally accepted RMPs...
October 8, 2016: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/27696908/decoding-p4-atpase-substrate-interactions
#14
Bartholomew P Roland, Todd R Graham
Cellular membranes display a diversity of functions that are conferred by the unique composition and organization of their proteins and lipids. One important aspect of lipid organization is the asymmetric distribution of phospholipids (PLs) across the plasma membrane. The unequal distribution of key PLs between the cytofacial and exofacial leaflets of the bilayer creates physical surface tension that can be used to bend the membrane; and like Ca(2+), a chemical gradient that can be used to transduce biochemical signals...
October 4, 2016: Critical Reviews in Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/27683659/dgk-%C3%AE-structure-enzymology-and-physiological-roles
#15
REVIEW
Becky Tu-Sekine, Hana L Goldschmidt, Daniel M Raben
Diacylglycerol kinases (DGKs) are a family of enzymes that catalyze the ATP-dependent phosphorylation of diacylglycerol (DAG) to phosphatidic acid (PtdOH). The recognition of the importance of these enzymes has been increasing ever since it was determined that they played a role in the phosphatidylinositol (PtdIns) cycle and a number of excellent reviews have already been written [(see van Blitterswijk and Houssa, 2000; Kanoh et al., 2002; Mérida et al., 2008; Tu-Sekine and Raben, 2009, 2011; Shulga et al...
2016: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/27681620/structure-guided-enzymology-of-the-lipid-a-acyltransferase-lpxm-reveals-a-dual-activity-mechanism
#16
Dustin Dovala, Christopher M Rath, Qijun Hu, William S Sawyer, Steven Shia, Robert A Elling, Mark S Knapp, Louis E Metzger
Gram-negative bacteria possess a characteristic outer membrane, of which the lipid A constituent elicits a strong host immune response through the Toll-like receptor 4 complex, and acts as a component of the permeability barrier to prevent uptake of bactericidal compounds. Lipid A species comprise the bulk of the outer leaflet of the outer membrane and are produced through a multistep biosynthetic pathway conserved in most Gram-negative bacteria. The final steps in this pathway involve the secondary acylation of lipid A precursors...
October 11, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27680509/preserving-enzymatic-activity-and-enhancing-biochemical-stability-of-glutathione-transferase-by-soluble-additives-under-free-and-tethered-conditions
#17
Christos S Karamitros, Nikolaos E Labrou
In the present study, we report on the effect of four different soluble additives (sucrose, lactitol, superfloc c577 and dextran sulphate) on the stability of the enzyme glutathione transferase 1 from Zea mays (ZmGSTF1-1) under free and tethered conditions at 4 and 25 °C. Among all additives, the best stabilizing effects observed in case of superfloc c577 and sucrose in both tested temperatures, yet at distinct concentrations at each condition. Those two stabilizing agents were further combined and potential positive synergistic effects were investigated...
September 28, 2016: Biotechnology and Applied Biochemistry
https://www.readbyqxmd.com/read/27670607/mechanistic-and-evolutionary-insights-from-comparative-enzymology-of-phosphomonoesterases-and-phosphodiesterases-across-the-alkaline-phosphatase-superfamily
#18
Fanny Sunden, Ishraq AlSadhan, Artem Y Lyubimov, Susanne Ressl, Helen Wiersma-Koch, Jamar Borland, Clayton L Brown, Tory A Johnson, Zorawar Singh, Daniel Herschlag
Naively one might have expected an early division between phosphate monoesterases and diesterases of the alkaline phosphatase (AP) superfamily. On the contrary, prior results and our structural and biochemical analyses of phosphate monoesterase PafA, from Chryseobacterium meningosepticum, indicate similarities to a superfamily phosphate diesterase [Xanthomonas citri nucleotide pyrophosphatase/phosphodiesterase (NPP)] and distinct differences from the three metal ion AP superfamily monoesterase, from Escherichia coli AP (EcAP)...
November 2, 2016: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/27650064/cell-biology-physiology-and-enzymology-of-phosphatidylserine-decarboxylase
#19
Francesca Di Bartolomeo, Ariane Wagner, Günther Daum
Phosphatidylethanolamine is one of the most abundant phospholipids whose major amounts are formed by phosphatidylserine decarboxylases (PSD). Here we provide a comprehensive description of different types of PSDs in the different kingdoms of life. In eukaryotes, type I PSDs are mitochondrial enzymes, whereas other PSDs are localized to other cellular compartments. We describe the role of mitochondrial Psd1 proteins, their function, enzymology, biogenesis, assembly into mitochondria and their contribution to phospholipid homeostasis in much detail...
September 17, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27640214/enzymology-in-chemical-toxicology-beyond-p450s
#20
Paul F Hollenberg
No abstract text is available yet for this article.
September 19, 2016: Chemical Research in Toxicology
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