Subsite cooperativity in protease specificity

2009 ◽  
Vol 390 (5/6) ◽  
Author(s):  
Natasha M. Ng ◽  
Robert N. Pike ◽  
Sarah E. Boyd
Keyword(s):  
Cell Cycle ◽  
Active Site ◽  
Negative Influence ◽  
Biological Processes ◽  
The Past ◽  
Wide Range ◽  
Cell Growth And Differentiation ◽  
Protease Specificity ◽  
Potential Methods ◽  
Protease Action

Abstract Proteases play vital roles in a range of biological processes, such as cell cycle, cell growth and differentiation, apoptosis, haemostasis and signalling. Fundamental to our knowledge of protease action is an understanding of how the active site operates; this has been examined through extensive studies of the substrate specificity of the enzymes. Kinetic and structural analyses have shown that the binding of a particular substrate residue at a protease subsite can have either a positive or negative influence on the binding of particular residues at other subsites. This phenomenon has been termed subsite cooperativity and has been observed in a wide range of proteases, often between non-adjacent subsites. This review aims to highlight studies where subsite cooperativity has been observed, experimental techniques used in the past and potential methods that can be employed to comprehensively examine this phenomenon. Further understanding of how the protease active site recognises and chooses its substrates for cleavage will have a significant impact on the development of pharmaceuticals that target these enzymes.

The Crosstalk between MicroRNAs and Gibberellin Signaling in Plants

2020 ◽  
Vol 61 (11) ◽  
pp. 1880-1890 ◽  
Author(s):  
Sha Yu ◽  
Jia-Wei Wang
Keyword(s):  
Target Genes ◽  
Floral Induction ◽  
Stem Elongation ◽  
Mirna Biogenesis ◽  
Biological Processes ◽  
Master Regulators ◽  
The Past ◽  
Della Proteins ◽  
Wide Range ◽  
Ga Response

Abstract Gibberellin (GA) is an integral phytohormone that plays prominent roles in controlling seed germination, stem elongation, leaf development and floral induction. It has been shown that GA regulates these diverse biological processes mainly through overcoming the suppressive effects of the DELLA proteins, a family of nuclear repressors of GA response. MicroRNAs (miRNAs), which have been identified as master regulators of gene expression in eukaryotes, are also involved in a wide range of plant developmental events through the repression of their target genes. The pathways of GA biosynthesis and signaling, as well as the pathways of miRNA biogenesis and regulation, have been profoundly delineated in the past several decades. Growing evidence has shown that miRNAs and GAs are coordinated in regulating plant development, as several components in GA pathways are targeted by miRNAs, and GAs also regulate the expression of miRNAs or their target genes vice versa. Here, we review the recent advances in our understanding of the molecular connections between miRNAs and GA, with an emphasis on the two miRNAs, miR156 and miR159.

Enhancing our understanding of the molecular responses to hypoxia in mammals using Drosophila melanogaster

2000 ◽  
Vol 88 (4) ◽  
pp. 1481-1487 ◽  
Author(s):  
Gabriel G. Haddad
Keyword(s):  
Drosophila Melanogaster ◽  
Neural Development ◽  
Genetic Model ◽  
Alcohol Intoxication ◽  
Biological Processes ◽  
Loss Of Function ◽  
Mutagenesis Screen ◽  
The Past ◽  
Wide Range ◽  
Or Gene

Drosophila melanogaster has been used as a genetic model, especially in the past decade, to examine normative biological processes and disease conditions very effectively. These span a wide range of major issues such as aging, cancer, embryogenesis, neural development, apoptosis, and alcohol intoxication. Here, we detail how the Drosophila melanogaster can be used as a genetic model to study the molecular and genetic underpinnings of the response to hypoxia. In our study of the basis of anoxia tolerance, one of the potent approaches that we use is a mutagenesis screen to identify loss-of-function mutants that are anoxia sensitive. The major advantage of this approach is that it is not biased for any particular gene or gene product. Although our screen is in progress, we already have evidence that this approach is useful.

Optical Properties of HVEM Accelerators

1975 ◽  
Vol 33 ◽  
pp. 180-181
Author(s):  
A. Strojnik ◽  
J.W. Scholl ◽  
V. Bevc
Keyword(s):  
Optical Properties ◽  
Electron Accelerator ◽  
Systematic Investigation ◽  
Electron Source ◽  
High Brightness ◽  
The Past ◽  
Wide Range ◽  
Optical Behavior

The electron accelerator, as inserted between the electron source (injector) and the imaging column of the HVEM, is usually a strong lens and should be optimized in order to ensure high brightness over a wide range of accelerating voltages and illuminating conditions. This is especially true in the case of the STEM where the brightness directly determines the highest resolution attainable. In the past, the optical behavior of accelerators was usually determined for a particular configuration. During the development of the accelerator for the Arizona 1 MEV STEM, systematic investigation was made of the major optical properties for a variety of electrode configurations, number of stages N, accelerating voltages, 1 and 10 MEV, and a range of injection voltages ϕ0 = 1, 3, 10, 30, 100, 300 kV).

Fluorescent potentiometric dyes for membrane-potential imaging

1994 ◽  
Vol 52 ◽  
pp. 166-167
Author(s):  
Leslie M. Loew
Keyword(s):  
Membrane Potential ◽  
Single Cells ◽  
Quantitative Imaging ◽  
Optical Recording ◽  
Biological Processes ◽  
Major Focus ◽  
The Past ◽  
Excitable Systems ◽  
Major Application ◽  
The Impact

A major application of potentiometric dyes has been the multisite optical recording of electrical activity in excitable systems. After being championed by L.B. Cohen and his colleagues for the past 20 years, the impact of this technology is rapidly being felt and is spreading to an increasing number of neuroscience laboratories. A second class of experiments involves using dyes to image membrane potential distributions in single cells by digital imaging microscopy - a major focus of this lab. These studies usually do not require the temporal resolution of multisite optical recording, being primarily focussed on slow cell biological processes, and therefore can achieve much higher spatial resolution. We have developed 2 methods for quantitative imaging of membrane potential. One method uses dual wavelength imaging of membrane-staining dyes and the other uses quantitative 3D imaging of a fluorescent lipophilic cation; the dyes used in each case were synthesized for this purpose in this laboratory.

Pursuit of the Abscopal Effect

2020 ◽  
Vol 04 (04) ◽  
pp. 369-372
Author(s):  
Paul B. Romesser ◽  
Christopher H. Crane
Keyword(s):  
Tumor Immunology ◽  
Antitumor Immunity ◽  
Clinical Success ◽  
Immune Recognition ◽  
Immune Modulators ◽  
Cancer Subtypes ◽  
The Past ◽  
Tumor Irradiation ◽  
Wide Range ◽  
Tumor Recognition

AbstractEvasion of immune recognition is a hallmark of cancer that facilitates tumorigenesis, maintenance, and progression. Systemic immune activation can incite tumor recognition and stimulate potent antitumor responses. While the concept of antitumor immunity is not new, there is renewed interest in tumor immunology given the clinical success of immune modulators in a wide range of cancer subtypes over the past decade. One particularly interesting, yet exceedingly rare phenomenon, is the abscopal response, characterized by a potent systemic antitumor response following localized tumor irradiation presumably attributed to reactivation of antitumor immunity.

The Many Pasts of Detective Fiction

2020 ◽  
Vol 1 (2) ◽  
pp. 157-172
Author(s):  
Thomas Leitch
Keyword(s):  
Detective Fiction ◽  
Golden Age ◽  
Public History ◽  
Detective Novel ◽  
Sherlock Holmes ◽  
Detective Story ◽  
The Past ◽  
Wide Range ◽  
Detective Novels ◽  
The Many

Building on Tzvetan Todorov's observation that the detective novel ‘contains not one but two stories: the story of the crime and the story of the investigation’, this essay argues that detective novels display a remarkably wide range of attitudes toward the several pasts they represent: the pasts of the crime, the community, the criminal, the detective, and public history. It traces a series of defining shifts in these attitudes through the evolution of five distinct subgenres of detective fiction: exploits of a Great Detective like Sherlock Holmes, Golden Age whodunits that pose as intellectual puzzles to be solved, hardboiled stories that invoke a distant past that the present both breaks with and echoes, police procedurals that unfold in an indefinitely extended present, and historical mysteries that nostalgically fetishize the past. It concludes with a brief consideration of genre readers’ own ambivalent phenomenological investment in the past, present, and future each detective story projects.

Nine Centuries of Man

2017 ◽  
Keyword(s):  
Twentieth Century ◽  
Diverse Range ◽  
Gender Expectations ◽  
Court Records ◽  
The Past ◽  
Wide Range ◽  
Police Reports ◽  
Late Twentieth ◽  
Scottish History ◽  
Late Twentieth Century

What did it mean to be a man in Scotland over the past nine centuries? Scotland, with its stereotypes of the kilted warrior and the industrial ‘hard man’, has long been characterised in masculine terms, but there has been little historical exploration of masculinity in a wider context. This interdisciplinary collection examines a diverse range of the multiple and changing forms of masculinities from the late eleventh to the late twentieth century, exploring the ways in which Scottish society through the ages defined expectations for men and their behaviour. How men reacted to those expectations is examined through sources such as documentary materials, medieval seals, romances, poetry, begging letters, police reports and court records, charity records, oral histories and personal correspondence. Focusing upon the wide range of activities and roles undertaken by men – work, fatherhood and play, violence and war, sex and commerce – the book also illustrates the range of masculinities that affected or were internalised by men. Together, the chapters illustrate some of the ways Scotland’s gender expectations have changed over the centuries and how, more generally, masculinities have informed the path of Scottish history

Free but fragile: Human relations amidst poverty and HIV in democratic South Africa

2015 ◽  
Vol 2 (2) ◽  
pp. 85-94
Author(s):  
Christina Landman
Keyword(s):  
South Africa ◽  
Predominantly White ◽  
Black People ◽  
Hiv Treatment ◽  
Human Relations ◽  
White People ◽  
Black And White ◽  
The Past ◽  
Wide Range ◽  
Black Township

Dullstroom-Emnotweni is the highest town in South Africa. Cold and misty, it is situated in the eastern Highveld, halfway between the capital Pretoria/Tswane and the Mozambique border. Alongside the main road of the white town, 27 restaurants provide entertainment to tourists on their way to Mozambique or the Kruger National Park. The inhabitants of the black township, Sakhelwe, are remnants of the Southern Ndebele who have lost their land a century ago in wars against the whites. They are mainly dependent on employment as cleaners and waitresses in the still predominantly white town. Three white people from the white town and three black people from the township have been interviewed on their views whether democracy has brought changes to this society during the past 20 years. Answers cover a wide range of views. Gratitude is expressed that women are now safer and HIV treatment available. However, unemployment and poverty persist in a community that nevertheless shows resilience and feeds on hope. While the first part of this article relates the interviews, the final part identifies from them the discourses that keep the black and white communities from forming a group identity that is based on equality and human dignity as the values of democracy.

Strongly Coupled Redox-Linked Conformational Switching at the Active Site of the Non-Heme Iron-Dependent Dioxygenase, TauD

2019 ◽  
Author(s):  
Christopher John ◽  
Greg M. Swain ◽  
Robert P. Hausinger ◽  
Denis A. Proshlyakov
Keyword(s):  
Active Site ◽  
Structural Model ◽  
Heme Iron ◽  
Chemical Transformations ◽  
Experimental Conditions ◽  
Strongly Coupled ◽  
Non Heme Iron ◽  
Reversible Redox ◽  
Wide Range ◽  
Complex Structural

2-Oxoglutarate (2OG)-dependent dioxygenases catalyze C-H activation while performing a wide range of chemical transformations. In contrast to their heme analogues, non-heme iron centers afford greater structural flexibility with important implications for their diverse catalytic mechanisms. We characterize an <i>in situ</i> structural model of the putative transient ferric intermediate of 2OG:taurine dioxygenase (TauD) by using a combination of spectroelectrochemical and semi-empirical computational methods, demonstrating that the Fe (III/II) transition involves a substantial, fully reversible, redox-linked conformational change at the active site. This rearrangement alters the apparent redox potential of the active site between -127 mV for reduction of the ferric state and 171 mV for oxidation of the ferrous state of the 2OG-Fe-TauD complex. Structural perturbations exhibit limited sensitivity to mediator concentrations and potential pulse duration. Similar changes were observed in the Fe-TauD and taurine-2OG-Fe-TauD complexes, thus attributing the reorganization to the protein moiety rather than the cosubstrates. Redox difference infrared spectra indicate a reorganization of the protein backbone in addition to the involvement of carboxylate and histidine ligands. Quantitative modeling of the transient redox response using two alternative reaction schemes across a variety of experimental conditions strongly supports the proposal for intrinsic protein reorganization as the origin of the experimental observations.

FROM THE HISTORY OF THE FORMATION AND DEVELOPMENT OF PERIODICALS IN NAMANGAN

2019 ◽  
Vol 20 (2) ◽  
pp. 49-54
Author(s):  
Dildora Alinazarova ◽  
Keyword(s):  
The Past ◽  
Wide Range ◽  
History Of ◽  
Printing House

In this article, based on an analysis of a wide range of sources, discusses the emergence and development of periodicals and printing house in Namangan. The activities of Ibrat- as the founder of the first printing house in Namangan are considered. In addition, it describes the functioning and development of "Matbaai Ishokia" in the past and present

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