Download or read book Bacillus Subtilis and Human Adenylosuccinate Lyase written by Sharmila Sivendran and published by ProQuest. This book was released on 2008 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Adenylosuccinate lyase is a homotetrameric enzyme that catalyzes two reversible reactions in the purine biosynthetic pathway. ASL deficiency results from several single point mutations which result in mild to severe mental retardation, muscle wasting and autistic features. Two novel point mutations, E80D and D87E, identified in an Australian patient, were characterized. Although one of the point mutations, E80D, is far from the active site, it seems to have a more detrimental effect on enzyme function as compared to D69E, which is found close to the active site. Mutagenesis studies of conserved residues in the active site have suggested that p K 2 of the pH-V max profile reflects the ionization of histidines. Conserved residues close to His 68 in the crystal structure, Asp 69 and Arg 310, when analyzed by mutagenesis, show that replacement of these charged residues with neutral residues results in greatly decreased activity, suggesting these residues are important for catalytic activity. When the same charge is maintained there is little change in p K 2 (indicating the His 68 proton is held tightly, as in WT), but when the charge is removed there is a decrease in p K 2 suggesting the His 68 proton is removed more easily. This shift in p K 2 supports the previous postulate that His 68 acts as the general acid. ASL catalyzes two similar reactions, questioning whether the two substrates occupy the same or different active sites. Studies with a new substrate analogue, adenosine phosphonobutyric acid, 2'(3'), 5'-diphosphate, show the two substrates occupy the same active site. Binding studies with this substrate analogue demonstrate that B. subtilis ASL has negative and human ASL has positive cooperativity in binding ligand. Binding studies of B. subtilis ASL inactive mutants show that these mutants bind the substrate analogue similarly to WT, indicating the replaced amino acids are important for catalysis (k cat) and not for binding substrate. Serines in the signature sequence region of the fumarase superfamily of enzymes, when mutated to determine the effect of these residues on activity, show that human Ser 289, B. subtilis Ser 262 and Ser 263 affect V max but not binding and that they may be interacting with the active sites.
Download or read book Bacillus Subtilis Adenylosuccinate Lyase written by Jennifer Brosius Palenchar and published by . This book was released on 2003 with total page 418 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Adenylosuccinate Lyases ASL from Bacillus Subtilis and Homo Sapiens written by Lushanti M. De Zoysa Ariyananda and published by . This book was released on 2011 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Adenylosuccinate lyase (ASL) belongs to the de novo purine biosynthesis pathway and the purine nucleotide cycle. It catalyses two reactions: conversion of SAICAR to AICAR and fumarate and conversion of adenylosuccinate to AMP and fumarate. ASL from all the species studied is a homotetramer in which three subunits contribute to each of four active sites. Human ASL deficiency is an inherited metabolic disease associated with autism and mental retardation. The majority of the missense mutations are compound heterozygous. In Chapter 2 we sought to evaluate the types of interactions responsible for subunit association of B. subtilis ASL. Perturbation of either hydrophobic or electrostatic interactions greatly destabilizes the tetramer of wild-type ASL and results in very low enzymatic activity. Accordingly, we mutated the closest charged residues located in the subunit interface that has the largest surface area. All the mutants have low V max values and decreased molecular weights. We conclude that both hydrophobic and electrostatic interactions play roles in maintaining the ASL tetramer and this structure is essential for adenylosuccinate lyase activity. Chapter 3 focuses on characterization of five disease-associated human ASL mutants located at different regions of the enzyme. Activity, stability of tetramer, and positive cooperativity of the mutant enzymes were reduced to different extents depending on the position in the enzyme. Thus, these disease-associated single mutations can yield enzyme with reduced activity either by affecting the active site or by perturbing the enzyme's structure and/or native conformation which are required for catalytic function. The possibility of forming hybrids in compound heterozygotes and separating the hybrids was assessed in Chapter 4. We were successful in forming various hybrids by denaturing the enzymes and renaturing by removing the denaturant, followed by separating the hybrids. There are favorable interactions between WT and mutant subunits, which accounts for the normal activity of ASL in the parents of ASL deficient patients, while the extent of interactions between two different mutant subunits depends upon the mutant enzymes. This implies that the presence of hybrids in parents of ASL deficient patients is highly advantageous, while it may not be true for severe ASL deficient patients.
Download or read book Characterization of Bacillus Subtilis Adenylosuccinate Lyase and Its Association with Glutamyl tRNA Synthetase written by Jack F. Quinlan and published by . This book was released on 1998 with total page 58 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Implication of 2 Histidines in the Active Site of Bacillus Subtilis Adenylosuccinate Lyase by Affinity Labeling Mutagenesis and Molecular Modeling written by Tom T. Lee and published by . This book was released on 1998 with total page 348 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Index Medicus written by and published by . This book was released on 2004 with total page 2098 pages. Available in PDF, EPUB and Kindle. Book excerpt: Vols. for 1963- include as pt. 2 of the Jan. issue: Medical subject headings.
Download or read book Biochemistry and Cell Biology of Artemia written by Thomas H. MacRae and published by CRC Press. This book was released on 2018-01-18 with total page 272 pages. Available in PDF, EPUB and Kindle. Book excerpt: The unusual life history of the brine shrimp, Artemia, and the relative ease with which it can be experimentally manipulated have long made his crustacean a favorite system for biological studies. Over the years, descriptive morphological work has given way to a rigorous analysis of biochemical and cellular aspects of the organism. The underlying theme of the work is often been developmental in nature.This book brings together a wide spectrum of topics under study in the shrimp. Analyses of gene structure and protein synthesis are combined with descriptions of protein interactions characteristic of functional cells.
Download or read book HNE and Further Lipid Peroxidation Products written by Werner Siems and published by IOS Press. This book was released on 2005 with total page 338 pages. Available in PDF, EPUB and Kindle. Book excerpt: Focuses on products of lipid peroxidation used as biomarkers of oxidative stress. This book covers the entire field of HNE research, including subjects as Cell Cycle and Proteolysis, LPO Products, Antioxidants and Detoxification, Neurodegeneration and Aging, Lipid Peroxidation, HNE and Gene Regulation, Clinical Applications and HNE, and more.
Download or read book Cumulated Index Medicus written by and published by . This book was released on 2000 with total page 1836 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Progress in Nucleic Acid Research and Molecular Biology written by and published by Academic Press. This book was released on 1992-05-22 with total page 305 pages. Available in PDF, EPUB and Kindle. Book excerpt: Progress in Nucleic Acid Research and Molecular Biology
Download or read book Basic Neurochemistry written by Scott T. Brady, PhD and published by Academic Press. This book was released on 2011-12-07 with total page 1122 pages. Available in PDF, EPUB and Kindle. Book excerpt: Includes bibliographical references and index.
Download or read book Enzymes Advances in Research and Application 2013 Edition written by and published by ScholarlyEditions. This book was released on 2013-06-21 with total page 696 pages. Available in PDF, EPUB and Kindle. Book excerpt: Enzymes—Advances in Research and Application: 2013 Edition is a ScholarlyEditions™ book that delivers timely, authoritative, and comprehensive information about Transferases. The editors have built Enzymes—Advances in Research and Application: 2013 Edition on the vast information databases of ScholarlyNews.™ You can expect the information about Transferases in this book to be deeper than what you can access anywhere else, as well as consistently reliable, authoritative, informed, and relevant. The content of Enzymes—Advances in Research and Application: 2013 Edition has been produced by the world’s leading scientists, engineers, analysts, research institutions, and companies. All of the content is from peer-reviewed sources, and all of it is written, assembled, and edited by the editors at ScholarlyEditions™ and available exclusively from us. You now have a source you can cite with authority, confidence, and credibility. More information is available at http://www.ScholarlyEditions.com/.
Download or read book Basic Neurochemistry written by R. Wayne Albers and published by Elsevier. This book was released on 2005-11-11 with total page 1020 pages. Available in PDF, EPUB and Kindle. Book excerpt: Basic Neurochemistry: Molecular, Cellular and Medical Aspects, a comprehensive text on neurochemistry, is now updated and revised in its Seventh Edition. This well-established text has been recognized worldwide as a resource for postgraduate trainees and teachers in neurology, psychiatry, and basic neuroscience, as well as for graduate and postgraduate students and instructors in the neurosciences. It is an excellent source of information on basic biochemical processes in brain function and disease for qualifying examinations and continuing medical education. Completely updated with 60% new authors and material, and entirely new chapters Over 400 fully revised figures in splendid color
Download or read book Class 1 Oxidoreductases III written by Dietmar Schomburg and published by Springer Science & Business Media. This book was released on 2004-03-23 with total page 544 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Springer Handbook of Enzymes provides concise data on some 5,000 enzymes sufficiently well characterized – and here is the second, updated edition. Their application in analytical, synthetic and biotechnology processes as well as in food industry, and for medicinal treatments is added. Data sheets are arranged in their EC-Number sequence. The new edition reflects considerable progress in enzymology: the total material has more than doubled, and the complete 2nd edition consists of 39 volumes plus Synonym Index. Starting in 2009, all newly classified enzymes are treated in Supplement Volumes.
Download or read book Dissertation Abstracts International written by and published by . This book was released on 2008 with total page 1006 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Purine and Pyrimidine Metabolism in Man IX written by Andrea Griesmacher and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 816 pages. Available in PDF, EPUB and Kindle. Book excerpt: th th This volume comprizes articles presented at the joint IX International and 6 Euro pean Symposium on Purine and Pyrimidine Metabolism in Man held in Gmunden, Austria, June 1 through 7, 1997. Since the first of this series of meetings was held in Israel in 1973, conventions were organized every three years in different parts of the world including the USA, Japan, and Europe. The different aspects of purine and pyrimidine metabolism bring together re searchers working in molecular genetics, biochemical pharmacology, biochemistry, devel opmental biology, immunology, epidemiology and the clinics. Oriented research in the field has been seminal for the development of potent anticancer and antiviral drugs. As the number of genes which are cloned, grows, the understanding of metabolism is increas ingly enlarged and might provide leads to further improve therapeutic concepts and to bet ter understand mechanisms responsible for the development of resistance against these drugs. In certain diseases purine and pyrimidine analogs represent not only the drugs of choice but in fact are the sole therapeutic alternative at present. The field has also taken an early lead in attempting to correct inborn errors of purine and pyrimidine metabolism by gene therapy. The organization of this meeting involved a large number of people who dedicated their time in an effort to make this symposium a success. We thank the Abstract Review Committee, the International Advisory Board and in particular the Symposium Secretariat for doing a wonderful job.
Download or read book Research Grants Index written by National Institutes of Health (U.S.). Division of Research Grants and published by . This book was released on 1967 with total page 974 pages. Available in PDF, EPUB and Kindle. Book excerpt: