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Author: Sulochanadevi Baskaran
Publisher:
ISBN:
Category : Glycogen
Languages : en
Pages : 272
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Book Description
Glycogen is a major energy reserve in most eukaryotes and its rate of synthesis is controlled by glycogen synthase. The activity of eukaryotic glycogen synthase is regulated by the allosteric activator glucose-6-phosphate, which can overcome the inhibitory effects of phosphorylation. The effects of phosphorylation and glucose-6-phosphate on glycogen synthase are mediated by a cluster of six arginines located within a stretch of 12 amino acids near the C-terminus of the enzyme's polypeptide chain. We studied isoform-2 of yeast glycogen synthase as a model to study the structural and molecular mechanisms that underlie the regulation of the eukaryotic enzymes and our primary tools of investigation were macromolecular X-ray crystallography, site-directed mutagenesis, intein-mediated peptide ligation and enzyme assays. We have solved the tetrameric structure of the yeast enzyme in two different activity states; the resting enzyme and the activated state when complexed with glucose-6-phosphate. Binding of glucose-6-phosphate to glycogen synthase induces large conformational changes that free the active site of the subunits to undergo conformational changes necessary to catalyze the reaction. Further, using site directed mutagenesis and intein-mediated peptide ligation to create specific phosphorylation states of the enzyme we were able to define specific roles for the arginine residues that mediate the regulatory effects of phosphorylation and glucose-6-phosphate activation. Based on these studies, we propose a three state structural model for the regulation of the enzyme, which relate the observed conformational states to specific activity levels. In addition to these regulatory studies, we have also solved the structure of the enzyme complexed with UDP and with substrate analogs, which provide detailed insight into the catalytic mechanism of the enzyme and the ability of glycogen synthase to remain tightly bound to its substrate glycogen.
Author: Sulochanadevi Baskaran
Publisher:
ISBN:
Category : Glycogen
Languages : en
Pages : 272
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Book Description
Glycogen is a major energy reserve in most eukaryotes and its rate of synthesis is controlled by glycogen synthase. The activity of eukaryotic glycogen synthase is regulated by the allosteric activator glucose-6-phosphate, which can overcome the inhibitory effects of phosphorylation. The effects of phosphorylation and glucose-6-phosphate on glycogen synthase are mediated by a cluster of six arginines located within a stretch of 12 amino acids near the C-terminus of the enzyme's polypeptide chain. We studied isoform-2 of yeast glycogen synthase as a model to study the structural and molecular mechanisms that underlie the regulation of the eukaryotic enzymes and our primary tools of investigation were macromolecular X-ray crystallography, site-directed mutagenesis, intein-mediated peptide ligation and enzyme assays. We have solved the tetrameric structure of the yeast enzyme in two different activity states; the resting enzyme and the activated state when complexed with glucose-6-phosphate. Binding of glucose-6-phosphate to glycogen synthase induces large conformational changes that free the active site of the subunits to undergo conformational changes necessary to catalyze the reaction. Further, using site directed mutagenesis and intein-mediated peptide ligation to create specific phosphorylation states of the enzyme we were able to define specific roles for the arginine residues that mediate the regulatory effects of phosphorylation and glucose-6-phosphate activation. Based on these studies, we propose a three state structural model for the regulation of the enzyme, which relate the observed conformational states to specific activity levels. In addition to these regulatory studies, we have also solved the structure of the enzyme complexed with UDP and with substrate analogs, which provide detailed insight into the catalytic mechanism of the enzyme and the ability of glycogen synthase to remain tightly bound to its substrate glycogen.
Author: Zao-Yuan Peng
Publisher:
ISBN:
Category :
Languages : en
Pages : 296
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Book Description
Author: Krishna Kishore Mahalingan
Publisher:
ISBN:
Category :
Languages : en
Pages : 250
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Book Description
Glycogen synthase (GS) is the rate limiting enzyme in the synthesis of glycogen. Eukaryotic GS catalyzes the transfer of glucose from UDP-glucose to the non-reducing ends of glycogen and its activity is negatively regulated by phosphorylation and allosterically activated by glucose-6-phosphate (G6P). A highly conserved cluster of six arginine residues on the C-terminal domain controls the responses toward these opposing signals. Previous studies had shown that tetrameric enzyme exists in three conformational states which are linked to specific structural changes in the regulatory helices that carry the cluster of arginines. These helices are found opposite and anti-parallel to one another at one of the subunit interfaces. The binding of G6P beneath the regulatory helices induces large scale conformational changes which open up the catalytic cleft for better substrate access. We solved the crystal structure of the enzyme in its inhibited state and found that the tetrameric and regulatory interfaces are more compacted compared to other states. The structural consequence of the tighter interfaces within the inhibited state of the tetramer is to lower the ability of glycogen chains to access to the catalytic cleft. Based on these observations, we developed a novel regulatory feature in yeast GS by substituting two of its conserved arginine residues on the regulatory helix with cysteines that permits its activity to be controlled by reversible oxidation/reduction of the cysteine residues which mimics the effects of reversible phosphorylation. In addition to defining the structural changes that give rise to the inhibited states, we also used X-ray crystallography to define the mechanism by which the enzyme discriminates between different UDP-sugar donors to be used as substrates in the catalytic mechanism of yeast GS. We found that only donor substrates can adopt the catalytically favorable bent conformation for donor transfer to a growing glycogen chain.
Author: Marilyn H. Meinke
Publisher:
ISBN:
Category :
Languages : en
Pages : 184
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Book Description
Author: Weiming Zhang
Publisher:
ISBN:
Category :
Languages : en
Pages : 212
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Book Description
Author: John Bruton Stanbury
Publisher:
ISBN:
Category : Medical
Languages : en
Pages : 1942
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Book Description
Author: Stefan Hohmann
Publisher: Springer Science & Business Media
ISBN: 3540456112
Category : Science
Languages : en
Pages : 398
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Book Description
Every cell has developed mechanisms to respond to changes in its environment and to adapt its growth and metabolism to unfavorable conditions. The unicellular eukaryote yeast has long proven as a particularly useful model system for the analysis of cellular stress responses, and the completion of the yeast genome sequence has only added to its power This volume comprehensively reviews both the basic features of the yeast genral stress response and the specific adapations to different stress types (nutrient depletion, osmotic and heat shock as well as salt and oxidative stress). It includes the latest findings in the field and discusses the implications for the analysis of stress response mechanisms in higher eukaryotes as well.
Author: John W. Pelley, PhD
Publisher: Elsevier Health Sciences
ISBN: 0323074464
Category : Medical
Languages : en
Pages : 254
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Book Description
Effectively merge basic science and clinical skills with Elsevier's Integrated Review Biochemistry, by John W. Pelley, PhD. This concise, high-yield title in the popular Integrated Review Series focuses on the core knowledge in biochemistry while linking that information to related concepts from other basic science disciplines. Case-based questions at the end of each chapter enable you to gauge your mastery of the material, and a color-coded format allows you to quickly find the specific guidance you need. Online access via www.studentconsult.com - included with your purchase - allows you to conveniently access the book's complete text and illustrations online as well as relevant content from other Student Consult titles. This concise and user-friendly reference provides crucial guidance for the early years of medical training and USMLE preparation. Spend more time reviewing and less time searching thanks to an extremely focused, "high-yield" presentation. Gauge your mastery of the material and build confidence with both case-based, andUSMLE-style questions that provide effective chapter review and quick practice for your exams. Access the full contents online at www.studentconsult.com where you'll find the complete text and illustrations, "Integration Links" to bonus content in other Student Consult titles, an interactive community center with a wealth of additional resources, and much more! Grasp and retain vital concepts more easily thanks to a color-coded format, succinct,text, key concept boxes, and dynamic illustrations that facilitate learning in a highly visual approach. Effectively review for problem-based courses with the help of text boxes that help you clearly see the clinical relevance of the material. Great for visual learners!
Author:
Publisher:
ISBN: 9780815332183
Category : Cells
Languages : en
Pages : 0
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Book Description
Author: Byung Hong Kim
Publisher: Cambridge University Press
ISBN: 1107171733
Category : Medical
Languages : en
Pages : 509
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Book Description
Extensive and up-to-date review of key metabolic processes in bacteria and archaea and how metabolism is regulated under various conditions.
