Download or read book Bottom up Design of Metalloprotein Assemblies with Diverse Metal Coordination Motifs and Emergent Properties written by Albert Kakkis and published by . This book was released on 2023 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Metal ions are indispensable to biological function, as they are utilized for a myriad of processes encompassing signaling, electron transfer, and catalysis. These functions are made possible by exploiting intrinsic properties of the metal ions and the ligands to which they bind, represented by small molecules and metalloproteins. From the perspective of a synthetic chemist, proteins can be conceived as "macromolecular ligands". Like those of small molecule ligands, the properties of "macromolecular ligands" can be parameterized at two discrete coordination spheres. The primary sphere is composed of the amino acid residues and exogenous ligands that coordinate the metal ion, and thus has the most direct impact on metal-based function. The secondary sphere is composed of residues that form mainly non-covalent interactions--hydrogen bonding, hydrophobic, and van der Waals (vDW) interactions--with the primary sphere. Although secondary sphere features do not directly bind the metal ion, they play an indispensable role in controlling metal-based reactivity. For example, the oxygen-binding affinity of myoglobin is influenced significantly by hydrogen bonding interactions between a histidine residue in its secondary sphere and the oxygen ligand that binds the heme co-factor. The large functional scope of metalloproteins is a testament to the wide diversity of primary and secondary spheres, and the efficiency with which metalloproteins execute these functions is a testament to the intricate interplay between the spheres. The functional potential of natural metalloproteins has long inspired protein design efforts. Two major metalloprotein design approaches are rational and de novo design. In rational design, primary and/or secondary sphere features of a natural protein are repurposed to mediate non-native functions. This approach has culminated in the engineering of new-to-nature functions spanning metal-hydride mediated ketone reduction and carbon-silicon bond coupling. While rational design represents an effective path to engineer metal-based functions, such functions are achieved within rigid and highly evolved protein folds/interfaces. Therefore, important questions remain unanswered: how does metal-based function emerge from an initially nonfunctional metalloprotein, and what are the minimum primary/secondary sphere coordination requirements to achieve metal-based functions? The work described in this dissertation stems from a de novo design approach in which both the quaternary structure and metal coordination site(s) of a metalloprotein are designed from scratch. The building block of our designed metalloprotein structures is cytochrome cb562, a natively monomeric, four-helix bundle protein. With cytochrome cb562 as our starting point, we obtain a diverse array of metalloprotein assemblies that serve as platforms for pursuing complex metal-based functions encompassing redox-based signaling and oxygen activation. In Chapter 2, we describe the sequential design of three metalloprotein trimers, TriCyt1, TriCyt2, and TriCyt3. TriCyt1, our initial trimeric construct, is obtained through a single hydrophobic mutation (G70W) at the interface of a cytochrome cb562 variant. Solution experiments indicated that TriCyt1 assembled as a trimer in the presence of all mid-to-late first row transition metals (MnII-ZnII), with yields ranging from 12% (+MnII) to 89% (+CoII). Crystal structures of NiII and CuII-supplemented TriCyt1 revealed a biologically rare His6 coordination motif. The only known natural His6 motif is present in calprotectin, a metal sequestering protein that coordinates MnII with nanomolar affinity. Motivated by the prospect of obtaining from scratch a MnII:His6 site of such high affinity, which had not yet been achieved in protein design, we sought to increase the preorganization of this metal coordination site through redesign of the C2 and C3 interfaces of TriCyt1. Computationally prescribed, mostly hydrophobic mutations at the C3 interface led to TriCyt2, a construct that trimerized with near-quantitative yield in the presence of MnII. A second round of redesign, in which salt bridges were installed at the C2 interface, led to a metal-independent, pH-switchable trimer which bound MnII with ~ 50 nM affinity. While a His6 primary sphere is suitable for achieving high affinity metal binding sites, our ability to design metalloproteins with broad functional potential hinges on our ability to engineer multiple types of metal binding sites. In Chapter 3, we describe our efforts to diversify the primary and/or secondary spheres of the TriCyt scaffold in pursuit of metalloprotein constructs which could coordinate lanthanides with high affinity and selectivity, mediate metal-dependent catalysis, and stabilize multinuclear metal coordination sites. The TriCyt series illustrates metal-ion-identity-independent assembly: the assembly path converges on the same architecture with the same metal coordination motif regardless of the metal ion added. In the TriCyt series there is low cooperativity between metal-ligand and non-covalent interactions, as metal coordination preferences play a minimal role in directing assembly. In Chapter 4, we describe our design and characterization of a variant of Rosetta interface design cytochrome 1 (A74/C96RIDC1) in which the cooperative interplay between metal-ligand and non-covalent interactions could be tuned by the redox state of the protein. In the oxidized state, C96-C96 disulfide bonds rigidify a tetrameric architecture (A74/C96RIDC14ox) whose assembly is independent of metal ion identity. Chemical reduction of the disulfide bonds gives rise to A74/C96RIDC1red, whose assembly is governed in larger part by the metal coordination preferences of exogenous metal ions. Whereas A74/C96RIDC14ox can only access two structural states (apo and metal-bound), A74/C96RIDC1red can access three distinct, metal-ion-identity dependent structural states with unique coordination environments. With five structural states whose accessibility is dependent on solution redox potential and metal ion identity, A74/C96RIDC1 represents a rare protein construct whose oligomerization path is varied through two different types of stimuli. We characterize the oligomeric and conformational states of A74/C96RIDC1 under disulfide-oxidized and disulfide-reduced states and in the presence of different mid-to-late first row transition metal ions, both in solution and via X-ray crystallography. We also employ density functional theory (DFT) and Rosetta interface calculations to attempt to quantify the energetic contributions of metal-ligand and non-covalent interactions and rationalize how differences in metal ion identity result in divergent metal-directed assembly paths.

Download or read book Biological Inorganic Chemistry written by Ivano Bertini and published by University Science Books. This book was released on 2007 with total page 794 pages. Available in PDF, EPUB and Kindle. Book excerpt: Part A.: Overviews of biological inorganic chemistry : 1. Bioinorganic chemistry and the biogeochemical cycles -- 2. Metal ions and proteins: binding, stability, and folding -- 3. Special cofactors and metal clusters -- 4. Transport and storage of metal ions in biology -- 5. Biominerals and biomineralization -- 6. Metals in medicine. -- Part B.: Metal ion containing biological systems : 1. Metal ion transport and storage -- 2. Hydrolytic chemistry -- 3. Electron transfer, respiration, and photosynthesis -- 4. Oxygen metabolism -- 5. Hydrogen, carbon, and sulfur metabolism -- 6. Metalloenzymes with radical intermediates -- 7. Metal ion receptors and signaling. -- Cell biology, biochemistry, and evolution: Tutorial I. -- Fundamentals of coordination chemistry: Tutorial II.

Download or read book Trace Metals and Infectious Diseases written by Jerome O. Nriagu and published by MIT Press. This book was released on 2024-06-11 with total page 501 pages. Available in PDF, EPUB and Kindle. Book excerpt: Experts explore the influence of trace metals on the pathogenesis of infectious diseases. Many parts of the world in which common infectious diseases are endemic also have the highest prevalence of trace metal deficiencies or rising rates of trace metal pollution. Infectious diseases can increase human susceptibility to adverse effects of metal exposure (at suboptimal or toxic levels), and metal excess or deficiency can increase the incidence or severity of infectious diseases. The co-clustering of major infectious diseases with trace metal deficiency or toxicity has created a complex web of interactions with serious but poorly understood health repercussions, yet has been largely overlooked in animal and human studies. This book focuses on the distribution, trafficking, fate, and effects of trace metals in biological systems. Its goal is to enhance our understanding of the relationships between homeostatic mechanisms of trace metals and the pathogenesis of infectious diseases. Drawing on expertise from a range of fields, the book offers a comprehensive review of current knowledge on vertebrate metal-withholding mechanisms and the strategies employed by different microbes to avoid starvation (or poisoning). Chapters summarize current, state-of-the-art techniques for investigating pathogen-metal interactions and highlight open question to guide future research. The book makes clear that improving knowledge in this area will be instrumental to the development of novel therapeutic measures against infectious diseases. Contributors M. Leigh Ackland, Vahid Fa Andisi, Angele L. Arrieta, Michael A. Bachman, J. Sabine Becker, Robert E. Black, Julia Bornhorst, Sascha Brunke, Joseph A. Caruso, Jennifer S. Cavet, Anson C. K. Chan, Christopher H. Contag, Heran Darwin, George V. Dedoussis, Rodney R. Dietert, Victor J. DiRita, Carol A. Fierke, Tamara Garcia-Barrera, David P. Giedroc, Peter-Leon Hagedoorn, James A. Imlay, Marek J. Kobylarz, Joseph Lemire, Wenwen Liu, Slade A. Loutet, Wolfgang Maret, Andreas Matusch, Trevor F. Moraes, Michael E. P. Murphy, Maribel Navarro, Jerome O. Nriagu, Ana-Maria Oros-Peusquens, Elisabeth G. Pacyna, Jozef M. Pacyna, Robert D. Perry, John M. Pettifor, Stephanie Pfaffen, Dieter Rehder, Lothar Rink, Anthony B. Schryvers, Ellen K. Silbergeld, Eric P. Skaar, Miguel C. P. Soares, Kyrre Sundseth, Dennis J. Thiele, Richard B. Thompson, Meghan M. Verstraete, Gonzalo Visbal, Fudi Wang, Mian Wang, Thomas J. Webster, Jeffrey N. Weiser, Günter Weiss, Inga Wessels, Bin Ye, Judith T. Zelikoff, Lihong Zhang

Download or read book Protein Folding and Metal Ions written by Cláudio M. Gomes and published by CRC Press. This book was released on 2016-04-19 with total page 302 pages. Available in PDF, EPUB and Kindle. Book excerpt: The role of metal ions in protein folding and structure is a critical topic to a range of scientists in numerous fields, particularly those working in structural biology and bioinorganic chemistry, those studying protein folding and disease, and those involved in the molecular and cellular aspects of metals in biological systems. Protein Folding an

Download or read book Comprehensive Asymmetric Catalysis written by Eric N. Jacobsen and published by Springer Science & Business Media. This book was released on 2003-09-22 with total page 258 pages. Available in PDF, EPUB and Kindle. Book excerpt: The first supplement to the three volume reference work "Comprehensive Asymmetric Catalysis" critically reviews new developments to the hottest topics in the field written by recognised experts. Eleven chapters which are already in the major reference work have been supplemented and additionally five new chapters have been included. Thus the state-of-the art in this area is now re-established. Together with the basic three volume book set this supplement is not only the principal reference source for synthetic organic chemists, but also for all scientific researchers who use chiral compounds in their work (for example, in biochemical investigations and molecular medicine) as well as for pharmaceutical chemists and other industrial researchers who prepare chiral compounds.

Download or read book Protein Self Assembly written by Jennifer J. McManus and published by Humana. This book was released on 2020-08-08 with total page 266 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume explores experimental and computational approaches to measuring the most widely studied protein assemblies, including condensed liquid phases, aggregates, and crystals. The chapters in this book are organized into three parts: Part One looks at the techniques used to measure protein-protein interactions and equilibrium protein phases in dilute and concentrated protein solutions; Part Two describes methods to measure kinetics of aggregation and to characterize the assembled state; and Part Three details several different computational approaches that are currently used to help researchers understand protein self-assembly. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Thorough and cutting-edge, Protein Self-Assembly: Methods and Protocols is a valuable resource for researchers who are interested in learning more about this developing field.

Download or read book Advances in Nanoengineering written by A. Giles Davies and published by Imperial College Press. This book was released on 2007 with total page 328 pages. Available in PDF, EPUB and Kindle. Book excerpt: Outlines a selection of advances made worldwide in the field of modern engineering at the nanometer scale. This work covers topics that include: the fabrication and measurement of nanoelectronic devices, organic conductors, and bioelectronic materials; the assembly of such structures into appropriate configurations; and more.

Download or read book Catalysis in Chemistry and Enzymology written by William P. Jencks and published by Courier Corporation. This book was released on 1987-01-01 with total page 866 pages. Available in PDF, EPUB and Kindle. Book excerpt: Exceptionally clear coverage of mechanisms for catalysis, forces in aqueous solution, carbonyl- and acyl-group reactions, practical kinetics, more.

Download or read book Nanozymes Next Wave of Artificial Enzymes written by Xiaoyu Wang and published by Springer. This book was released on 2016-07-27 with total page 134 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book describes the fundamental concepts, the latest developments and the outlook of the field of nanozymes (i.e., the catalytic nanomaterials with enzymatic characteristics). As one of today’s most exciting fields, nanozyme research lies at the interface of chemistry, biology, materials science and nanotechnology. Each of the book’s six chapters explores advances in nanozymes. Following an introduction to the rise of nanozymes research in the course of research on natural enzymes and artificial enzymes in Chapter 1, Chapters 2 through 5 discuss different nanomaterials used to mimic various natural enzymes, from carbon-based and metal-based nanomaterials to metal oxide-based nanomaterials and other nanomaterials. In each of these chapters, the nanomaterials’ enzyme mimetic activities, catalytic mechanisms and key applications are covered. In closing, Chapter 6 addresses the current challenges and outlines further directions for nanozymes. Presenting extensive information on nanozymes and supplemented with a wealth of color illustrations and tables, the book offers an ideal guide for readers from disparate areas, including analytical chemistry, materials science, nanoscience and nanotechnology, biomedical and clinical engineering, environmental science and engineering, green chemistry, and novel catalysis.

Download or read book Bionanotechnology written by David S. Goodsell and published by John Wiley & Sons. This book was released on 2004-04-16 with total page 351 pages. Available in PDF, EPUB and Kindle. Book excerpt: Discussions of the basic structural, nanotechnology, and system engineering principles, as well as an introductory overview of essential concepts and methods in biotechnology, will be included. Text is presented side-by-side with extensive use of high-quality illustrations prepared using cutting edge computer graphics techniques. Includes numerous examples, such applications in genetic engineering. Represents the only available introduction and overview of this interdisciplinary field, merging the physical and biological sciences. Concludes with the authors' expert assessment of the future promise of nanotechnology, from molecular "tinkertoys" to nanomedicine. David Goodsell is author of two trade books, Machinery of Life and Our Molecular Nature, and Arthur Olson is the world's leader in molecular graphics and nano-scale representation.

Download or read book Beyond the Molecular Frontier written by National Research Council and published by National Academies Press. This book was released on 2003-03-19 with total page 238 pages. Available in PDF, EPUB and Kindle. Book excerpt: Chemistry and chemical engineering have changed significantly in the last decade. They have broadened their scopeâ€"into biology, nanotechnology, materials science, computation, and advanced methods of process systems engineering and controlâ€"so much that the programs in most chemistry and chemical engineering departments now barely resemble the classical notion of chemistry. Beyond the Molecular Frontier brings together research, discovery, and invention across the entire spectrum of the chemical sciencesâ€"from fundamental, molecular-level chemistry to large-scale chemical processing technology. This reflects the way the field has evolved, the synergy at universities between research and education in chemistry and chemical engineering, and the way chemists and chemical engineers work together in industry. The astonishing developments in science and engineering during the 20th century have made it possible to dream of new goals that might previously have been considered unthinkable. This book identifies the key opportunities and challenges for the chemical sciences, from basic research to societal needs and from terrorism defense to environmental protection, and it looks at the ways in which chemists and chemical engineers can work together to contribute to an improved future.

Download or read book Protein protein Recognition written by Colin Kleanthous and published by Frontiers in Molecular Biology. This book was released on 2000 with total page 370 pages. Available in PDF, EPUB and Kindle. Book excerpt: The purpose of Protein-Protein Recognition is to bring together concepts and systems pertaining to protein-protein interactions in a single unifying volume. In the light of the information from the genome sequencing projects and the increase in structural information it is an opportune time totry to make generalizations about how and why proteins form complexes with each other. The emphasis of the book is on heteromeric complexes (complexes in which each of the components can exist in an unbound state) and will use well-studied model systems to explain the processes of formingcomplexes. After an introductory section on the kinetics, thermodynamics, analysis, and classification of protein-protein interactions, weak, intermediate, and high affinity complexes are dealt with in turn. Weak affinity complexes are represented by electron transfer proteins and integrincomplexes. Anti-lysozyme antibodies, the MHC proteins and their interactions with T-cell receptors, and the protein interactions of eukaryotic signal transduction are the systems used to explain complexes with intermediate affinities. Finally, tight binding complexes are represented by theinteraction of protein inhibitors with serine proteases and by nuclease inhibitor complexes. Throughout the chapters common themes are the technologies which have had the greatest impact, how specificity is determined, how complexes are stabilized, and medical and industrial applications.

Download or read book Innovations and Implementations of Computer Aided Drug Discovery Strategies in Rational Drug Design written by Sanjeev Kumar Singh and published by Springer Nature. This book was released on 2021-02-02 with total page 334 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book presents various computer-aided drug discovery methods for the design and development of ligand and structure-based drug molecules. A wide variety of computational approaches are now being used in various stages of drug discovery and development, as well as in clinical studies. Yet, despite the rapid advances in computer software and hardware, combined with the exponential growth in the available biological information, there are many challenges that still need to be addressed, as this book shows. In turn, it shares valuable insights into receptor-ligand interactions in connection with various biological functions and human diseases. The book discusses a wide range of phylogenetic methods and highlights the applications of Molecular Dynamics Simulation in the drug discovery process. It also explores the application of quantum mechanics in order to provide better accuracy when calculating protein-ligand binding interactions and predicting binding affinities. In closing, the book provides illustrative descriptions of major challenges associated with computer-aided drug discovery for the development of therapeutic drugs. Given its scope, it offers a valuable asset for life sciences researchers, medicinal chemists and bioinformaticians looking for the latest information on computer-aided methodologies for drug development, together with their applications in drug discovery.

Download or read book Bioinorganic Chemistry written by Rosette M. Roat-Malone and published by John Wiley & Sons. This book was released on 2007-10-05 with total page 544 pages. Available in PDF, EPUB and Kindle. Book excerpt: An updated, practical guide to bioinorganic chemistry Bioinorganic Chemistry: A Short Course, Second Edition provides the fundamentals of inorganic chemistry and biochemistry relevant to understanding bioinorganic topics. Rather than striving to provide a broad overview of the whole, rapidly expanding field, this resource provides essential background material, followed by detailed information on selected topics. The goal is to give readers the background, tools, and skills to research and study bioinorganic topics of special interest to them. This extensively updated premier reference and text: Presents review chapters on the essentials of inorganic chemistry and biochemistry Includes up-to-date information on instrumental and analytical techniques and computer-aided modeling and visualization programs Familiarizes readers with the primary literature sources and online resources Includes detailed coverage of Group 1 and 2 metal ions, concentrating on biological molecules that feature sodium, potassium, magnesium, and calcium ions Describes proteins and enzymes with iron-containing porphyrin ligand systems-myoglobin, hemoglobin, and the ubiquitous cytochrome metalloenzymes-and the non-heme, iron-containing proteins aconitase and methane monooxygenase Appropriate for one-semester bioinorganic chemistry courses for chemistry, biochemistry, and biology majors, this text is ideal for upper-level undergraduate and beginning graduate students. It is also a valuable reference for practitioners and researchers who need a general introduction to bioinorganic chemistry, as well as chemists who want an accessible desk reference.

Download or read book Bioremediation of Salt Affected Soils An Indian Perspective written by Sanjay Arora and published by Springer. This book was released on 2017-03-31 with total page 316 pages. Available in PDF, EPUB and Kindle. Book excerpt: This edited volume focuses on the characterization, reclamation, bioremediation, and phytoremediation of salt affected soils and waterlogged sodic soils. Innovative technologies in managing marginal salt affected lands merit immediate attention in the light of climate change and its impact on crop productivity and environment. The decision-making process related to reclamation and management of vast areas of salt affected soils encompasses consideration of economic viability, environmental sustainability, and social acceptability of different approaches. The chapters in this book highlight the significant environmental and social impacts of different ameliorative techniques used to manage salt affected soils. Readers will discover new knowledge on the distribution, reactions, changes in bio-chemical properties and microbial ecology of salt affected soils through case studies exploring Indian soils. The contributions presented by experts shed new light on techniques such as the restoration of degraded lands by growing halophyte plant species, diversification of crops and introduction of microbes for remediation of salt infested soils, and the use of fluorescent pseudomonads for enhancing crop yields.

Download or read book Lymphedema written by Byung-Boong Lee and published by Springer. This book was released on 2018-01-10 with total page 939 pages. Available in PDF, EPUB and Kindle. Book excerpt: The second edition of this book serves as a central source of theoretical and practical knowledge to optimize the evaluation and treatment of patients with lymphedema. The book covers all aspects of the disease from anatomical and histological features to diagnosis as well as physical/medical and surgical management of the disease. Updated from the first edition to reflect the substantial progress in diagnostics, medical care and surgical intervention for this patient population, this volume has been reorganized to meet today’s practice requirements. It addresses the challenges faced by clinicians in the management of chronic lymphedema enabling them to meet the medical needs of this large patient community. Edited by world leaders in Vascular Medicine and Surgery, this comprehensive volume provides clear, concise background and recommendations in an easy-to-use format. It is a valuable reference tool for clinical practitioners (physicians/nurse practitioners/technicians) who wish to deliver state-of-the-art health care to their patients with lymphatic and venous disorders.

Download or read book Dental Caries written by Zhou Xuedong and published by Springer. This book was released on 2015-10-20 with total page 187 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book is a well-illustrated and comprehensive guide to the etiology, clinical manifestations, diagnosis, clinical management and prevention of dental caries. Current challenging problems in the field are analyzed and the latest research findings, presented. After an introductory chapter on tooth development, the relationships of biofilm and saliva to dental caries and the significance of the balance between demineralization and remineralization for the development of carious lesions are discussed. Subsequent chapters address the state of the art in diagnosis and treatment, the implications of disease burden for prevention and the association between systemic diseases and dental caries. Dental Caries: Principles and Management is intended for dental school students, practicing dentists and researchers in dentistry.