scholarly journals Crystal structure of human mARC1 reveals its exceptional position among eukaryotic molybdenum enzymes

2018 ◽  
Vol 115 (47) ◽  
pp. 11958-11963 ◽  
Author(s):  
Christian Kubitza ◽  
Florian Bittner ◽  
Carsten Ginsel ◽  
Antje Havemeyer ◽  
Bernd Clement ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Catalytic Mechanism ◽  
Full Range ◽  
3D Structure ◽  
Cytochrome P450 Enzymes ◽  
Oxygenated Compounds ◽  
Online Databases ◽  
Starting Point ◽  
Wide Range ◽  
Nitrogen Containing Compounds

Biotransformation enzymes ensure a viable homeostasis by regulating reversible cycles of oxidative and reductive reactions. The metabolism of nitrogen-containing compounds is of high pharmaceutical and toxicological relevance because N-oxygenated metabolites derived from reactions mediated by cytochrome P450 enzymes or flavin-dependent monooxygenases are in some cases highly toxic or mutagenic. The molybdenum-dependent mitochondrial amidoxime-reducing component (mARC) was found to be an extremely efficient counterpart, which is able to reduce the full range of N-oxygenated compounds and thereby mediates detoxification reactions. However, the 3D structure of this enzyme was unknown. Here we present the high-resolution crystal structure of human mARC. We give detailed insight into the coordination of its molybdenum cofactor (Moco), the catalytic mechanism, and its ability to reduce a wide range of N-oxygenated compounds. The identification of two key residues will allow future discrimination between mARC paralogs and ensure correct annotation. Since our structural findings contradict in silico predictions that are currently made by online databases, we propose domain definitions for members of the superfamily of Moco sulfurase C-terminal (MOSC) domain-containing proteins. Furthermore, we present evidence for an evolutionary role of mARC for the emergence of the xanthine oxidase protein superfamily. We anticipate the hereby presented crystal structure to be a starting point for future descriptions of MOSC proteins, which are currently poorly structurally characterized.

Crystal structure images of large gold clusters and growing crystals by HRTEM

1984 ◽  
Vol 42 ◽  
pp. 428-429
Author(s):  
L.R. Wallenberg ◽  
J.-O. Bovin ◽  
G. Schmid
Keyword(s):  
Crystal Structure ◽  
Nucleation And Growth ◽  
Close Packing ◽  
Gold Clusters ◽  
Molecular Weight Determination ◽  
Growth Mechanisms ◽  
Starting Point ◽  
Different Types ◽  
Nucleation And Growth Mechanisms ◽  
Points Of View

Metallic clusters are interesting from various points of view, e.g. as a mean of spreading expensive catalysts on a support, or following heterogeneous and homogeneous catalytic events. It is also possible to study nucleation and growth mechanisms for crystals with the cluster as known starting point.Gold-clusters containing 55 atoms were manufactured by reducing (C6H5)3PAuCl with B2H6 in benzene. The chemical composition was found to be Au9.2[P(C6H5)3]2Cl. Molecular-weight determination by means of an ultracentrifuge gave the formula Au55[P(C6H5)3]Cl6 A model was proposed from Mössbauer spectra by Schmid et al. with cubic close-packing of the 55 gold atoms in a cubeoctahedron as shown in Fig 1. The cluster is almost completely isolated from the surroundings by the twelve triphenylphosphane groups situated in each corner, and the chlorine atoms on the centre of the 3x3 square surfaces. This gives four groups of gold atoms, depending on the different types of surrounding.

Discovery of Antibacterial Agents Inhibiting the Energy-Coupling Factor (ECF) Transporters by Structure-Based Virtual Screening

2020 ◽  
Author(s):  
Eleonora Diamanti ◽  
Inda Setyawati ◽  
Spyridon Bousis ◽  
leticia mojas ◽  
lotteke Swier ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Antibacterial Agents ◽  
Antimicrobial Agents ◽  
Energy Coupling ◽  
Coupling Factor ◽  
Design Synthesis ◽  
Screening Design ◽  
Starting Point ◽  
Wide Range ◽  
Vitamin Uptake

Here, we report on the virtual screening, design, synthesis and structure–activity relationships (SARs) of the first class of selective, antibacterial agents against the energy-coupling factor (ECF) transporters. The ECF transporters are a family of transmembrane proteins involved in the uptake of vitamins in a wide range of bacteria. Inhibition of the activity of these proteins could reduce the viability of pathogens that depend on vitamin uptake. Because of their central role in the metabolism of bacteria and their absence in humans, ECF transporters are novel potential antimicrobial targets to tackle infection. The hit compound’s metabolic and plasma stability, the potency (20, MIC Streptococcus pneumoniae = 2 µg/mL), the absence of cytotoxicity and a lack of resistance development under the conditions tested here suggest that this scaffold may represent a promising starting point for the development of novel antimicrobial agents with an unprecedented mechanism of action.<br>

The Major Transitions in Evolution

1997 ◽  
Author(s):  
John Maynard Smith ◽  
Eors Szathmary
Keyword(s):  
Full Range ◽  
Evolution Of Cooperation ◽  
Major Transitions ◽  
Insect Societies ◽  
Wide Range ◽  
Major Transition ◽  
Life Itself ◽  
History Of ◽  
Emergence Of Cooperation ◽  
Multicellular Organisms

Over the history of life there have been several major changes in the way genetic information is organized and transmitted from one generation to the next. These transitions include the origin of life itself, the first eukaryotic cells, reproduction by sexual means, the appearance of multicellular plants and animals, the emergence of cooperation and of animal societies, and the unique language ability of humans. This ambitious book provides the first unified discussion of the full range of these transitions. The authors highlight the similarities between different transitions--between the union of replicating molecules to form chromosomes and of cells to form multicellular organisms, for example--and show how understanding one transition sheds light on others. They trace a common theme throughout the history of evolution: after a major transition some entities lose the ability to replicate independently, becoming able to reproduce only as part of a larger whole. The authors investigate this pattern and why selection between entities at a lower level does not disrupt selection at more complex levels. Their explanation encompasses a compelling theory of the evolution of cooperation at all levels of complexity. Engagingly written and filled with numerous illustrations, this book can be read with enjoyment by anyone with an undergraduate training in biology. It is ideal for advanced discussion groups on evolution and includes accessible discussions of a wide range of topics, from molecular biology and linguistics to insect societies.

Oxford Studies in Medieval Philosophy Volume 7

2019 ◽  
Keyword(s):  
Late Antiquity ◽  
Full Range ◽  
Current Work ◽  
Medieval Philosophy ◽  
Original Essays ◽  
Wide Range ◽  
Extended Review

Oxford Studies in Medieval Philosophy annually collects the best current work in the field of medieval philosophy. The various volumes print original essays, reviews, critical discussions, and editions of texts. The aim is to contribute to an understanding of the full range of themes and problems in all aspects of the field, from late antiquity into the Renaissance, and extending over the Jewish, Islamic, and Christian traditions. Volume 6 includes work on a wide range of topics, including Davlat Dadikhuda on Avicenna, Christopher Martin on Abelard’s ontology, Jeremy Skrzypek and Gloria Frost on Aquinas’s ontology, Jean‐Luc Solère on instrumental causality, Peter John Hartman on Durand of St.‐Pourçain, and Kamil Majcherek on Chatton’s rejection of final causality. The volume also includes an extended review of Thomas Williams of a new book on Aquinas’s ethics by Colleen McCluskey.

scholarly journals Characterisation of nitrogen-containing organic compounds by UHPLC-Qtof-MS and anti-amylase activity from the chloroform extract of the bark of Rhizophora mucronata

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
P. Resmi ◽  
G. Jitha ◽  
Vishnu Murali ◽  
Anu Gopinath
Keyword(s):  
Diabetes Mellitus ◽  
Amylase Activity ◽  
Chloroform Extract ◽  
Significant Activity ◽  
Rhizophora Mucronata ◽  
Inhibition Assay ◽  
Mangrove Plant ◽  
Starting Point ◽  
Treatment Of Diabetes ◽  
Nitrogen Containing Compounds

Abstract Background Medicinal importance of mangrove plant Rhizophora mucronata, a red mangrove species found in the Asian countries, has long been recognised in traditional systems of medicine. The identification of its phytoconstituents can be a starting point for the drug development. The aim of the work was to extend the current knowledge of phytoconstituents from R. mucronata and to explore its pharmacological importance in the treatment of diabetes mellitus. In the present study, we analysed the chloroform extract from the bark of the mangrove plant R. mucronata for nitrogen-containing constituents using UHPLC QTOF MS profiling, and α-amylase inhibition assay was carried out. Results Four nitrogen-containing compounds were identified from the chloroform extract of the bark of R. mucronata using UHPLC QTOF MS profiling. The compounds identified were N,N′-dicyclohexyl urea, a cryptolepine derivative (C17H15N3O), an aliphatic cyclic compound with hydroxyl and amino groups (C22H43NO), and C16H19NO2 (m/z 258.1495). The anti-amylase activity, an in vitro antidiabetic bioassay, of chloroform extract showed an IC50 value of 220.09 μg/ml. Conclusions This is the first report on the identification of nitrogen-containing compounds from the chloroform extract of the bark of the R. Mucronata. One of the compounds identified was a novel cryptolepine derivative (C16H13N3O), and it falls under the rare category indoloquinoline alkaloid. The chloroform extract also showed significant activity towards α-amylase inhibition assay. Thus, the study has gone some way towards our understanding of the efficacy of bark of the R. mucronata for the treatment of diabetes mellitus and is open for further research.

scholarly journals Consumer Neuroscience Techniques in Advertising Research: A Bibliometric Citation Analysis

2021 ◽  
Vol 13 (3) ◽  
pp. 1589
Author(s):  
Juan Sánchez-Fernández ◽  
Luis-Alberto Casado-Aranda ◽  
Ana-Belén Bastidas-Manzano
Keyword(s):  
Self Report ◽  
Future Research ◽  
Complex Nature ◽  
Clear Understanding ◽  
Continuous Growth ◽  
Main Research ◽  
Consumer Neuroscience ◽  
Starting Point ◽  
Wide Range ◽  
Performance Analysis Tools

The limitations of self-report techniques (i.e., questionnaires or surveys) in measuring consumer response to advertising stimuli have necessitated more objective and accurate tools from the fields of neuroscience and psychology for the study of consumer behavior, resulting in the creation of consumer neuroscience. This recent marketing sub-field stems from a wide range of disciplines and applies multiple types of techniques to diverse advertising subdomains (e.g., advertising constructs, media elements, or prediction strategies). Due to its complex nature and continuous growth, this area of research calls for a clear understanding of its evolution, current scope, and potential domains in the field of advertising. Thus, this current research is among the first to apply a bibliometric approach to clarify the main research streams analyzing advertising persuasion using neuroimaging. Particularly, this paper combines a comprehensive review with performance analysis tools of 203 papers published between 1986 and 2019 in outlets indexed by the ISI Web of Science database. Our findings describe the research tools, journals, and themes that are worth considering in future research. The current study also provides an agenda for future research and therefore constitutes a starting point for advertising academics and professionals intending to use neuroimaging techniques.

scholarly journals Chemical Synthesis and NMR Solution Structure of Conotoxin GXIA from Conus geographus

Marine Drugs ◽  
2021 ◽  
Vol 19 (2) ◽  
pp. 60
Author(s):  
David A. Armstrong ◽  
Ai-Hua Jin ◽  
Nayara Braga Emidio ◽  
Richard J. Lewis ◽  
Paul F. Alewood ◽  
...  
Keyword(s):  
Solution Structure ◽  
3D Structure ◽  
Voltage Sensor ◽  
Solution Nmr ◽  
Striking Similarity ◽  
Amino Acid Peptide ◽  
Wide Range ◽  
Cone Snails ◽  
Drug Leads ◽  
Β Sheet

Conotoxins are disulfide-rich peptides found in the venom of cone snails. Due to their exquisite potency and high selectivity for a wide range of voltage and ligand gated ion channels they are attractive drug leads in neuropharmacology. Recently, cone snails were found to have the capability to rapidly switch between venom types with different proteome profiles in response to predatory or defensive stimuli. A novel conotoxin, GXIA (original name G117), belonging to the I3-subfamily was identified as the major component of the predatory venom of piscivorous Conus geographus. Using 2D solution NMR spectroscopy techniques, we resolved the 3D structure for GXIA, the first structure reported for the I3-subfamily and framework XI family. The 32 amino acid peptide is comprised of eight cysteine residues with the resultant disulfide connectivity forming an ICK+1 motif. With a triple stranded β-sheet, the GXIA backbone shows striking similarity to several tarantula toxins targeting the voltage sensor of voltage gated potassium and sodium channels. Supported by an amphipathic surface, the structural evidence suggests that GXIA is able to embed in the membrane and bind to the voltage sensor domain of a putative ion channel target.

scholarly journals Structural basis of Naa20 activity towards a canonical NatB substrate

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Dominik Layer ◽  
Jürgen Kopp ◽  
Miriam Fontanillo ◽  
Maja Köhn ◽  
Karine Lapouge ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Drug Development ◽  
Catalytic Mechanism ◽  
Peptide Binding ◽  
Competitive Inhibitor ◽  
Structural Basis ◽  
Substrate Affinity ◽  
Protein Homeostasis ◽  
Auxiliary Subunit

AbstractN-terminal acetylation is one of the most common protein modifications in eukaryotes and is carried out by N-terminal acetyltransferases (NATs). It plays important roles in protein homeostasis, localization, and interactions and is linked to various human diseases. NatB, one of the major co-translationally active NATs, is composed of the catalytic subunit Naa20 and the auxiliary subunit Naa25, and acetylates about 20% of the proteome. Here we show that NatB substrate specificity and catalytic mechanism are conserved among eukaryotes, and that Naa20 alone is able to acetylate NatB substrates in vitro. We show that Naa25 increases the Naa20 substrate affinity, and identify residues important for peptide binding and acetylation activity. We present the first Naa20 crystal structure in complex with the competitive inhibitor CoA-Ac-MDEL. Our findings demonstrate how Naa20 binds its substrates in the absence of Naa25 and support prospective endeavors to derive specific NAT inhibitors for drug development.

Energy-minimization multiscale based mesoscale modeling and applications in gas-fluidized catalytic reactors

2019 ◽  
Vol 35 (8) ◽  
pp. 879-915 ◽  
Author(s):  
Bona Lu ◽  
Yan Niu ◽  
Feiguo Chen ◽  
Nouman Ahmad ◽  
Wei Wang ◽  
...  
Keyword(s):  
Energy Minimization ◽  
Fluid Model ◽  
Scale Up ◽  
Flow Characteristics ◽  
Chemical Kinetic ◽  
Mesoscale Modeling ◽  
Catalytic Reactors ◽  
Chemical Kinetic Model ◽  
Starting Point ◽  
Wide Range

Abstract Gas-solid fluidization is intrinsically dynamic and manifests mesoscale structures spanning a wide range of length and timescales. When involved with reactions, more complex phenomena emerge and thus pose bigger challenges for modeling. As the mesoscale is critical to understand multiphase reactive flows, which the conventional two-fluid model without mesoscale modeling may be inadequate to resolve even using extremely fine grids, this review attempts to demonstrate that the energy-minimization multiscale (EMMS) model could be a starting point to develop such mesoscale modeling. Then, the EMMS-based mesoscale modeling with emphasis on formulation of drag coefficients for different fluidization regimes, modification of mass transfer coefficient, and other extensions are discussed in an attempt to resolve the emerging challenges. Its applications with examples of development of novel fluid catalytic cracking and methanol-to-olefins processes prove that the mesoscale modeling plays a remarkable role in improving the predictions in hydrodynamic behaviors and overall reaction rate. However, the product content primarily depends on the chemical kinetic model itself, suggesting the necessity of an effective coupling between chemical kinetics and flow characteristics. The mesoscale modeling can be believed to accelerate the traditional experimental-based scale-up process with much lower cost in the future.

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