Kinetic and Mechanistic Studies of Oxygen Sensing Fe(II)/2-oxoglutarate Dependent Oxygenases
Title | Kinetic and Mechanistic Studies of Oxygen Sensing Fe(II)/2-oxoglutarate Dependent Oxygenases PDF eBook |
Author | Hanna Tarhonskaya |
Publisher | |
Pages | |
Release | 2014 |
Genre | |
ISBN |
Mechanistic Studies on 2-oxoglutarate Dependent Oxygenases
Title | Mechanistic Studies on 2-oxoglutarate Dependent Oxygenases PDF eBook |
Author | Andrea Szollossi |
Publisher | |
Pages | |
Release | 2012 |
Genre | |
ISBN |
2-Oxoglutarate-Dependent Oxygenases
Title | 2-Oxoglutarate-Dependent Oxygenases PDF eBook |
Author | Christopher Schofield |
Publisher | Royal Society of Chemistry |
Pages | 508 |
Release | 2015-04-23 |
Genre | Science |
ISBN | 1782621954 |
Since the discovery of the first examples of 2-oxoglutarate-dependent oxygenase-catalysed reactions in the 1960s, a remarkably broad diversity of alternate reactions and substrates has been revealed, and extensive advances have been achieved in our understanding of the structures and catalytic mechanisms. These enzymes are important agrochemical targets and are being pursued as therapeutic targets for a wide range of diseases including cancer and anemia. This book provides a central source of information that summarizes the key features of the essential group of 2-oxoglutarate-dependent dioxygenases and related enzymes. Given the numerous recent advances and biomedical interest in the field, this book aims to unite the latest research for those already working in the field as well as to provide an introduction for those newly approaching the topic, and for those interested in translating the basic science into medicinal and agricultural benefits. The book begins with four broad chapters that highlight critical aspects, including an overview of possible catalytic reactions, structures and mechanisms. The following seventeen chapters focus on carefully selected topics, each written by leading experts in the area. Readers will find explanations of rapidly evolving research, from the chemistry of isopenicillin N synthase to the oxidation mechanism of 5-methylcytosine in DNA by ten-eleven-translocase oxygenases.
Structural and Mechanistic Studies of the Iron(II)- and 2-oxoglutarate-dependent Dioxygenases
Title | Structural and Mechanistic Studies of the Iron(II)- and 2-oxoglutarate-dependent Dioxygenases PDF eBook |
Author | Edward Longbotham |
Publisher | |
Pages | |
Release | 2014 |
Genre | |
ISBN |
Selective Inhibition and Mechanistic Studies of the Human O2 Sensor, Prolyl Hydroxylase Domain 2 (PHD2)
Title | Selective Inhibition and Mechanistic Studies of the Human O2 Sensor, Prolyl Hydroxylase Domain 2 (PHD2) PDF eBook |
Author | Shannon Coates Flagg |
Publisher | |
Pages | 98 |
Release | 2011 |
Genre | Oxygen in the body |
ISBN |
Prolyl Hydroxylase Domain 2 (PHD2) has been identified as a key oxygen sensor in humans along with Factor Inhibiting Hypoxia Inducible Factor (FIH). As such PHD2 and FIH play critical roles in myriad pathways of medical relevance by hydroxylation of their target substrate hypoxia inducible factor (HIF), a transcription factor responsible for the regulation of over 100+ genes. With such critical roles in human physiology the ability to selectively regulate these two enzymes could potentially lead the way for novel therapeutic treatments of a vast array of disease states from cancer to myocardial infarction. We report on three classes of iron chelators which show promise for independent regulation of the HIF hydroxylases. Compounds representing the pyrones/pyridinones, pyridines and catechols were tested and found to have differential impacts on PHD2 and FIH under the same experimental conditions. The mode of inhibition is the result of binding to the active site iron and is supported by UV-visible and electroparamagnetic resonance spectroscopy. PHD2 at the current time does not have a well resolved mechanistic understanding regarding its catalytic cycle and subsequent rate determining steps. We have employed pH, solvent isotope, and X-ray absorption studies in an effort to gain further understanding regarding PHD2's overall mechanism. Our data support that dissociation of an iron(II)-OH2 bond centered about the active site contributes to a portion of the overall rate determining steps in the catalytic reaction of PHD2 that activates oxygen and ends with the production of hydroxylated substrate.
Natural Product Biosynthesis
Title | Natural Product Biosynthesis PDF eBook |
Author | Christopher T. Walsh |
Publisher | Royal Society of Chemistry |
Pages | 787 |
Release | 2017-04-28 |
Genre | Science |
ISBN | 1788010760 |
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.
Iron-containing Enzymes
Title | Iron-containing Enzymes PDF eBook |
Author | Sam P. De Visser |
Publisher | Royal Society of Chemistry |
Pages | 463 |
Release | 2011 |
Genre | Science |
ISBN | 1849731810 |
Mononuclear iron containing enzymes are important intermediates in bioprocesses and have potential in the industrial biosynthesis of specific products. This book features topical review chapters by leaders in this field and its various sub-disciplines.