The Approach To Characterizing Three S Adenosyl L Methionine Dependent Methyltransferases From Mycobacterium Tuberculosis
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The Approach To Characterizing Three S Adenosyl L Methionine Dependent Methyltransferases From Mycobacterium Tuberculosis
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Author : Gwendal Loarer
language : en
Publisher:
Release Date : 2018
The Approach To Characterizing Three S Adenosyl L Methionine Dependent Methyltransferases From Mycobacterium Tuberculosis written by Gwendal Loarer and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2018 with Adenosylmethionine categories.
Tuberculosis (TB) remains a global health threat, especially due to the emergence and rapid evolution of resistant strains of pathogenic bacteria coupled to the lack of development in treatment. The main treatment requires infected individuals to take multiple drugs over an extended period of time. The treatment for individuals infected with strains of TB that are resistant to classic antibiotics is even heavier. The main drugs have remained the same over the past 50 years and more efficient drugs against TB are yet to be discovered. The development of new and more efficient drugs is therefore becoming increasingly urgent. Mycobacterium tuberculosis, the causative agent of TB, is particularly difficult to kill because of the thick and highly hydrophobic cell wall. 6-O-Methylglucose lipopolysaccharides (MGLP) have a major role in the biosynthesis of fatty acids and mycolic acids. Mycolic acids are one of the main reasons for the hydrophobicity and efficiency of the cell wall in protecting the bacteria. Disrupting the synthesis of MGLP shows significant decrease in growth and bacterial activity of Mtb. Rv3030 is an S-Adenosyl-L-Methionine (SAM)-dependent methyltransferase (MTase) and is a major enzyme in the biosynthetic pathway of MGLP as it is responsible for the essential 6-O- methylation. Unfortunately, the information currently available on this protein is limited as no crystal structure has been published. Therefore, to suppress the production of MGLP through the inhibition of Rv3030, it is necessary to fully characterize Rv3030. In order to achieve this goal, we screened compounds against Rv3030 using Differential Scanning Fluorimetry (DSF) to obtain information on chemotypes that could potentially be used as a basis for the development of Rv3030 inhibitors. Additionally, we used a competitive fluorescence polarization (FP) assay to measure in vitro activity of Rv3030, which would allow for inhibitor validation studies. In parallel, Rv3030 was crystallized in an initial screen and will provide valuable information leading crystal structure determination. The second part of this thesis focuses on the characterization of an enzyme essential for the survival of Mtb within the host. Rv1405 is an uncharacterized putative SAM- dependent MTase for which the function remains at the stage of hypothesis. This part describes the steps we have taken to obtain information on this enzyme screening multiple libraries of compounds using a DSF assay and optimizing a competitive FP assay to carry out inhibitory studies. In an attempt to gain invaluable structural knowledge of Rv1405, we obtained preliminary crystals of Rv1405 establishing a basis for further improvement of crystallization. The last part of this thesis describes the work and experiments carried out to characterize Rv0893 and confirm that it is a SAM-dependent MTase. Knowledge about this enzyme is extremely limited, making the study of Rv0893 to be challenging. We have used DSF and competitive FP assays with the intention to identify the biological methyl acceptor of this enzyme. In parallel, we crystallized and attempted to optimize crystallization in an attempt to gain valuable structural knowledge about Rv0893.
Radical Sam Enzymes
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Author :
language : en
Publisher: Academic Press
Release Date : 2018-08-09
Radical Sam Enzymes written by and has been published by Academic Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2018-08-09 with Science categories.
Radical SAM Enzymes, Volume 606, the latest release in the Methods in Enzymology series, highlights new advances in the field, with this new volume presenting interesting chapters on the Characterization of the glycyl radical enzyme choline trimethylamine-lyase and its radical S-adenosylmethionine activating enzyme, Diphathimide biosynthesis, Radical SAM glycyl radical activating enzymes, Radical SAM enzyme BioB in the biosynthesis of biotin, Biogenesis of the PQQ cofactor, Role of MoaAC in the biogenesis of the molybdenum cofactor, Biosynthesis of the nitrogenase cofactor, Bioinformatics of the radical SAM superfamily, The involvement of SAM radical enzymes in the biosynthesis of methanogenic coenzymes, methanopterin and coenzyme F420, and more.
Cumulated Index Medicus
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Author :
language : en
Publisher:
Release Date : 1977
Cumulated Index Medicus written by and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 1977 with Medicine categories.
The Ribosome
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Author : Roger A. Garrett
language : en
Publisher: Amer Society for Microbiology
Release Date : 2000
The Ribosome written by Roger A. Garrett and has been published by Amer Society for Microbiology this book supported file pdf, txt, epub, kindle and other format this book has been release on 2000 with Medical categories.
Complete coverage of the ribosome and mechanisms of protein synthesis. * Examines the structure and function of numerous extra-chromosomal factors. * Offers the first detailed account of crystal structures of the ribosome as well as insights into the mechanisms and action of antibiotics. This title is published by the American Society for Microbiology Press and distributed by Taylor and Francis in rest of world territories.
Molecular Genetics Of Mycobacteria
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Author : Graham F. Hatfull
language : en
Publisher: John Wiley & Sons
Release Date : 2014-09-02
Molecular Genetics Of Mycobacteria written by Graham F. Hatfull and has been published by John Wiley & Sons this book supported file pdf, txt, epub, kindle and other format this book has been release on 2014-09-02 with Science categories.
A comprehensive collection of perspectives by experts in mycobacterial molecular biology Mycobacterium tuberculosis causes one in four avoidable deaths in the developing world and kills more adults than malaria, AIDS, and all tropical diseases combined. Tuberculosis was named a global health emergency by the World Health Organization, a distinction no other disease has received. Although the study of mycobacterial genetics has expanded dramatically, with new investigations into mycobacterial growth, replication, metabolism, physiology, drug susceptibility, and virulence, most of the problems in tuberculosis control that existed in 2000 remain today. Advances in our understanding of mycobacterial genetics have been reflected in exciting recent developments. New diagnostic approaches can identify drug resistance within a few hours, promising new drugs are progressing through the pipeline and into the clinic, and a range of newly developed vaccines are being evaluated. It is an exciting time as the fruits of 30 years of intensive genetic investigation are finally beginning to emerge. Written by leading experts in the field, Molecular Genetics of Mycobacteria, Second Edition, Discusses key areas of current research in mycobacterial genetics Explains the genetics of the physiology, metabolism, and drug sensitivities of M. tuberculosis Presents genetic approaches for manipulating M. tuberculosis This book is an invaluable resource for anyone interested in the molecular genetics and molecular biology of mycobacteria.
Homocysteine In Health And Disease
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Author : Ralph Carmel
language : en
Publisher: Cambridge University Press
Release Date : 2001-07-19
Homocysteine In Health And Disease written by Ralph Carmel and has been published by Cambridge University Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2001-07-19 with Medical categories.
This is an unusually comprehensive 2001 account of the broad range of medical implications of homocysteine.
Fluorine And Health
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Author : Alain Tressaud
language : en
Publisher: Elsevier
Release Date : 2008-06-06
Fluorine And Health written by Alain Tressaud and has been published by Elsevier this book supported file pdf, txt, epub, kindle and other format this book has been release on 2008-06-06 with Medical categories.
Fluorine and Health presents a critical multidisciplinary overview on the contribution of fluorinated compounds to resolve the important global issue of medicinal monitoring and health care. The involved subjects are organized in three thematic parts devoted to Molecular Imaging, Biomedical Materials and Pharmaceuticals. Initially the key-position of partially fluorinated low molecular weight compounds labelled either with the natural 19F-isotope for Magnetic Resonance Imaging (MRI) or labelled with the radioactive [18F]-isotope for Positron Emission Tomography (PET) is highlighted. Both non-invasive methods belong to the most challenging in vivo imaging techniques in oncology, neurology and in cardiology for the diagnosis of diseases having the highest mortality in the industrialized countries. The manifold facets of fluorinated biomaterials range from inorganic ceramics to perfluorinated organic molecules. Liquid perfluorocarbons are suitable for oxygen transport and as potential respiratory gas carriers, while fluorinated polymers are connected to the pathology of blood vessels. Another important issue concerns the application of highly fluorinated liquids in ophthalmology. Moreover, fluorine is an essential trace element in bone mineral, dentine and tooth enamel and is applied for the prophylaxis and treatment of dental caries. The various origins of human exposure to fluoride species is detailed to promote a better understanding of the effect of fluoride species on living organisms.Medicinally relevant fluorinated molecules and their interactions with native proteins are the main focus of the third part. New molecules fluorinated in strategic position are crucial for the development of pharmaceuticals with desired action and optimal pharmacological profile. Among the hundreds of marketed active drug components there are more than 150 fluorinated compounds. The chapters will illustrate how the presence of fluorine atoms alters properties of bioactive compounds at various biochemical steps, and possibly facilitate its emergence as pharmaceuticals. Finally the synthetic potential of a fluorinase, the first C-F bond forming enzyme, is summarized. New approach of topics involving chemistry, biology and medicinal techniques Transdisciplinar papers on fluoride products Importance of fluoride products in health Updated data on specific topics
S Adenosylmethionine Dependent Methyltransferases Structures And Functions
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Author : Robert M Blumenthal
language : en
Publisher: World Scientific
Release Date : 1999-07-23
S Adenosylmethionine Dependent Methyltransferases Structures And Functions written by Robert M Blumenthal and has been published by World Scientific this book supported file pdf, txt, epub, kindle and other format this book has been release on 1999-07-23 with Science categories.
This invaluable volume, written by an international group of scientists, presents an overview of the AdoMet-dependent methyltransferases, with special emphasis on structure-function relationships.S-adenosyl-L-methionine (AdoMet) is the second most commonly used enzyme cofactor after ATP. The AdoMet-dependent methyltransferases act on a wide variety of target molecules, including DNA, RNA, protein, polysaccharides, lipids and a range of small molecules.The well-conserved architecture of these enzymes, and the implications of this conservation for their evolutionary history, are major themes of this book. The thirteen chapters describe in detail the structures, enzyme kinetics and biological roles of the AdoMet-dependent methyltransferases from a wide range of cell types: plant, animal, bacterial and archaeal.
Natural Product Biosynthesis
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Author : Christopher T. Walsh
language : en
Publisher: Royal Society of Chemistry
Release Date : 2017-04-28
Natural Product Biosynthesis written by Christopher T. Walsh and has been published by Royal Society of Chemistry this book supported file pdf, txt, epub, kindle and other format this book has been release on 2017-04-28 with Science categories.
This textbook describes the types of natural products, the biosynthetic pathways that enable the production of these molecules, and an update on the discovery of novel products in the post-genomic era.
Dna Methyltransferases Role And Function
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Author : Albert Jeltsch
language : en
Publisher: Springer
Release Date : 2016-11-08
Dna Methyltransferases Role And Function written by Albert Jeltsch and has been published by Springer this book supported file pdf, txt, epub, kindle and other format this book has been release on 2016-11-08 with Science categories.
DNA methyltransferases are important enzymes in a broad range of organisms. Dysfunction of DNA methyltransferases in humans leads to many severe diseases, including cancer. This book focuses on the biochemical properties of these enzymes, describing their structures and mechanisms in bacteria, humans and other species, including plants, and also explains the biological processes of reading of DNA methylation and DNA demethylation. It covers many emerging aspects of the biological roles of DNA methylation functioning as an essential epigenetic mark and describes the role of DNA methylation in diseases. Moreover, the book explains modern technologies, like targeted rewriting of DNA methylation by designed DNA methyltransferases, as well as technological applications of DNA methyltransferases in DNA labelling. Finally, the book summarizes recent methods for the analysis of DNA methylation in human DNA. Overall, this book represents a comprehensive state-of-the-art- work and is a must-have for advanced researchers in the field of DNA methylation and epigenetics.