Structure-function Analysis of the Ribonuclease-H Domain of Human Immunodeficiency Virus Type-1 Reverse Transcriptase

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ISBN 13 :
Total Pages : 350 pages
Book Rating : 4.:/5 (339 download)

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Book Synopsis Structure-function Analysis of the Ribonuclease-H Domain of Human Immunodeficiency Virus Type-1 Reverse Transcriptase by : Nick Mario Cirino

Download or read book Structure-function Analysis of the Ribonuclease-H Domain of Human Immunodeficiency Virus Type-1 Reverse Transcriptase written by Nick Mario Cirino and published by . This book was released on 1995 with total page 350 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Analysis of the Ribonuclease H Activity of Human Immunodeficiency Virus Type 1 Reverse Transcriptase

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ISBN 13 :
Total Pages : 400 pages
Book Rating : 4.:/5 (41 download)

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Book Synopsis Analysis of the Ribonuclease H Activity of Human Immunodeficiency Virus Type 1 Reverse Transcriptase by : Jeffrey S. Smith

Download or read book Analysis of the Ribonuclease H Activity of Human Immunodeficiency Virus Type 1 Reverse Transcriptase written by Jeffrey S. Smith and published by . This book was released on 1994 with total page 400 pages. Available in PDF, EPUB and Kindle. Book excerpt:

HIV-1 Integrase

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Publisher : John Wiley & Sons
ISBN 13 : 1118015363
Total Pages : 710 pages
Book Rating : 4.1/5 (18 download)

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Book Synopsis HIV-1 Integrase by : Nouri Neamati

Download or read book HIV-1 Integrase written by Nouri Neamati and published by John Wiley & Sons. This book was released on 2011-08-10 with total page 710 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book comprehensively covers the mechanisms of action and inhibitor design for HIV-1 integrase. It serves as a resource for scientists facing challenging drug design issues and researchers in antiviral drug discovery. Despite numerous review articles and isolated book chapters dealing with HIV-1 integrase, there has not been a single source for those working to devise anti-AIDS drugs against this promising target. But this book fills that gap and offers a valuable introduction to the field for the interdisciplinary scientists who will need to work together to design drugs that target HIV-1 integrase.

Human Immunodeficiency Virus Reverse Transcriptase

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Publisher : Springer Science & Business Media
ISBN 13 : 1461472911
Total Pages : 358 pages
Book Rating : 4.4/5 (614 download)

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Book Synopsis Human Immunodeficiency Virus Reverse Transcriptase by : Stuart LeGrice

Download or read book Human Immunodeficiency Virus Reverse Transcriptase written by Stuart LeGrice and published by Springer Science & Business Media. This book was released on 2013-07-23 with total page 358 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Reverse Transcriptase (RT) of Human Immunodeficiency Virus Type 1 (HIV-1) arguably ranks amongst one of the most extensively studied retroviral enzymes. Heterologous expression and purification of HIV-1 RT in the early eighties, approval of the first nucleoside analogue RT inhibitor (NRTI) in 1987, discovery of resistance to RT inhibitors, approval of the first non-nucleoside analogue RT inhibitor (NNRTI) in 1996 and the various crystal structures of RT with and without bound substrate(s) and/or inhibitors represent only a few of the important milestones that describe the a bench-to-bedside success in the continuing effort to combat HIV-1 infection and its consequences. Nucleoside and nonnucleoside RT inhibitors remain important components in frequently used drug regimens to treat the infection. RT inhibitors also play important roles in recently validated strategies to prevent transmission of the virus. The relevance of HIV-1 RT as a drug target has simultaneously triggered interest in basic research studies aimed at providing a more detailed understanding of interactions between proteins, nucleic acids, and small molecule ligands in general terms. In light of the ever-growing knowledge on structure and function of HIV-1 RT, this enzyme serves as a valuable “model system” in efforts to develop novel experimental tools and to explain biochemical processes. This monograph is designed to provide an overview of important aspects in past and current HIV-1 RT research, with focus on mechanistic aspects and translation of knowledge into drug discovery and development. The first section includes chapters with emphasis placed on the coordination of the RT-associated DNA polymerase and ribonuclease H (RNase H) activities. The second covers mechanisms of action and future perspectives associated with NRTIs and NNRTIs, while the third section includes chapters focusing on novel strategies to target the RT enzyme. Chapters of the final part are intended to discuss mechanisms involved in HIV variability and the development of drug resistance. We hope that these contributions will stimulate interest, and encourage research aimed at the development of novel RT inhibitors. The lack of bona fide RNase H inhibitors with potent antiviral activity provides an example for challenges and opportunities in the field.

The Ribonuclease H of Human Immunodeficiency Virus

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ISBN 13 :
Total Pages : 396 pages
Book Rating : 4.:/5 (89 download)

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Book Synopsis The Ribonuclease H of Human Immunodeficiency Virus by : Jen Ron Chiang

Download or read book The Ribonuclease H of Human Immunodeficiency Virus written by Jen Ron Chiang and published by . This book was released on 1994 with total page 396 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Structure-function Studies on the Human Immunodeficiency Virus Type 1 Reverse Transcriptase

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ISBN 13 :
Total Pages : 328 pages
Book Rating : 4.:/5 (835 download)

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Book Synopsis Structure-function Studies on the Human Immunodeficiency Virus Type 1 Reverse Transcriptase by : Michael Rostam Bavand

Download or read book Structure-function Studies on the Human Immunodeficiency Virus Type 1 Reverse Transcriptase written by Michael Rostam Bavand and published by . This book was released on 1993 with total page 328 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Ribonucleases H

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ISBN 13 : 9782855985978
Total Pages : 265 pages
Book Rating : 4.9/5 (859 download)

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Book Synopsis Ribonucleases H by : Robert J.. Crouch

Download or read book Ribonucleases H written by Robert J.. Crouch and published by . This book was released on 1998-01-01 with total page 265 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Proteins: Structure, Function, and Engineering

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Publisher : Springer Science & Business Media
ISBN 13 : 1489917276
Total Pages : 451 pages
Book Rating : 4.4/5 (899 download)

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Book Synopsis Proteins: Structure, Function, and Engineering by : B.B. Biswas

Download or read book Proteins: Structure, Function, and Engineering written by B.B. Biswas and published by Springer Science & Business Media. This book was released on 2013-06-29 with total page 451 pages. Available in PDF, EPUB and Kindle. Book excerpt: Here, researchers review the latest breakthroughs in protein research. Their contributions explore emerging principles and techniques and survey important classes of proteins that will play key roles in the field's future. Articles examine the possibility of a Boltzman-like distribution in protein substructures, the new technique of Raman spectroscopy, and compact intermediate states of protein folding. This well-illustrated volume also features coverage of proteins that bind nucleic acids.

Nucleic Acid Polymerases

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Publisher : Springer Science & Business Media
ISBN 13 : 3642397964
Total Pages : 342 pages
Book Rating : 4.6/5 (423 download)

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Book Synopsis Nucleic Acid Polymerases by : Katsuhiko S. Murakami

Download or read book Nucleic Acid Polymerases written by Katsuhiko S. Murakami and published by Springer Science & Business Media. This book was released on 2013-10-22 with total page 342 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides a review of the multitude of nucleic acid polymerases, including DNA and RNA polymerases from Archea, Bacteria and Eukaryota, mitochondrial and viral polymerases, and other specialized polymerases such as telomerase, template-independent terminal nucleotidyl transferase and RNA self-replication ribozyme. Although many books cover several different types of polymerases, no book so far has attempted to catalog all nucleic acid polymerases. The goal of this book is to be the top reference work for postgraduate students, postdocs, and principle investigators who study polymerases of all varieties. In other words, this book is for polymerase fans by polymerase fans. Nucleic acid polymerases play a fundamental role in genome replication, maintenance, gene expression and regulation. Throughout evolution these enzymes have been pivotal in transforming life towards RNA self-replicating systems as well as into more stable DNA genomes. These enzymes are generally extremely efficient and accurate in RNA transcription and DNA replication and share common kinetic and structural features. How catalysis can be so amazingly fast without loss of specificity is a question that has intrigued researchers for over 60 years. Certain specialized polymerases that play a critical role in cellular metabolism are used for diverse biotechnological applications and are therefore an essential tool for research.

Investigating the Functional Interaction Between Human Immunodeficiency Virus Type 1 Integrase and Reverse Transcripts and the Mechanism by which Integrase Influences the Early Events of Reverse Transcription

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ISBN 13 :
Total Pages : 414 pages
Book Rating : 4.:/5 ( download)

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Book Synopsis Investigating the Functional Interaction Between Human Immunodeficiency Virus Type 1 Integrase and Reverse Transcripts and the Mechanism by which Integrase Influences the Early Events of Reverse Transcription by : Charles Warren Dobard

Download or read book Investigating the Functional Interaction Between Human Immunodeficiency Virus Type 1 Integrase and Reverse Transcripts and the Mechanism by which Integrase Influences the Early Events of Reverse Transcription written by Charles Warren Dobard and published by . This book was released on 2007 with total page 414 pages. Available in PDF, EPUB and Kindle. Book excerpt:

The Structural Dynamics of Human Immunodeficiency Virus Type I Reverse Transcriptase

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ISBN 13 :
Total Pages : 168 pages
Book Rating : 4.:/5 (115 download)

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Book Synopsis The Structural Dynamics of Human Immunodeficiency Virus Type I Reverse Transcriptase by : James Malcolm Seckler

Download or read book The Structural Dynamics of Human Immunodeficiency Virus Type I Reverse Transcriptase written by James Malcolm Seckler and published by . This book was released on 2011 with total page 168 pages. Available in PDF, EPUB and Kindle. Book excerpt: Human Immunodeficiency Virus Type 1 Reverse Transcriptase (RT) is the protein in HIV responsible for transcribing viral RNA into double stranded DNA, making it an essential component in viral infectivity and the most popular target for anti-viral therapies for HIV. Over the years, a plethora of inhibitors for RT have been developed, and many of them are currently approved for clinical use. Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI) are small molecules that act as non-competitive, allosteric inhibitors of RT, binding in a binding pocket inside of the polymerase domain of RT and hampering enzymatic activity. Although this is a widely used class of viral inhibitor, the mechanism of inhibition is currently unknown. In addition to this, most current knowledge of RT is concentrated on the heterodimer, while little is known of the monomeric precursors to this structure. In this study we employ HXMS and SAXS to probe the solution structural dynamics and solution structure of RT heterodimer and monomers. We show that the p51 subunit does not form the stable core of the protein. Rather the core consists of the fingers and palm subdomains of both subunits. A ß-sheet that forms half of the NNRTI binding site undergoes slow cooperative unfolding, which is slowed by several orders of magnitude upon NNRTI binding. In addition to this, HXMS analysis reveals an allosteric network of regions that spans both subunits of the RT heterodimer. This network is thought to play a vital role in RT inhibition. The structural dynamics and solution structure of RT monomers were determined, revealing that the monomers were structured but more flexible in solution compared to the solution structure of the heterodimer. HXMS revealed that the monomers had nearly identical secondary structure, with the main difference being slow cooperative unfolding in the p66 thumb subdomain. SAXS revealed that both monomers exist in an ensemble of conformation. The polymerase domain of both monomers exists both in an open p66-like conformation, a closed p51-like conformation, and several unique conformations. This research lays the foundation for a novel method of drug screening and discovery.

Recoding: Expansion of Decoding Rules Enriches Gene Expression

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Publisher : Springer Science & Business Media
ISBN 13 : 0387893822
Total Pages : 473 pages
Book Rating : 4.3/5 (878 download)

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Book Synopsis Recoding: Expansion of Decoding Rules Enriches Gene Expression by : John F. Atkins

Download or read book Recoding: Expansion of Decoding Rules Enriches Gene Expression written by John F. Atkins and published by Springer Science & Business Media. This book was released on 2010-03-10 with total page 473 pages. Available in PDF, EPUB and Kindle. Book excerpt: The literature on recoding is scattered, so this superb book ?lls a need by prov- ing up-to-date, comprehensive, authoritative reviews of the many kinds of recoding phenomena. Between 1961 and 1966 my colleagues and I deciphered the genetic code in Escherichia coli and showed that the genetic code is the same in E. coli, Xenopus laevis, and guinea pig tissues. These results showed that the code has been c- served during evolution and strongly suggested that the code appeared very early during biological evolution, that all forms of life on earth descended from a c- mon ancestor, and thus that all forms of life on this planet are related to one another. The problem of biological time was solved by encoding information in DNA and retrieving the information for each new generation, for it is easier to make a new organism than it is to repair an aging, malfunctioning one. Subsequently, small modi?cations of the standard genetic code were found in certain organisms and in mitochondria. Mitochondrial DNA only encodes about 10–13 proteins, so some modi?cations of the genetic code are tolerated that pr- ably would be lethal if applied to the thousands of kinds of proteins encoded by genomic DNA.

Characterizing Human Immunodeficiency Virus Type 1 Reverse Transcriptase and Integrase Interaction

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ISBN 13 :
Total Pages : 83 pages
Book Rating : 4.:/5 (89 download)

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Book Synopsis Characterizing Human Immunodeficiency Virus Type 1 Reverse Transcriptase and Integrase Interaction by : Shewit Tekeste

Download or read book Characterizing Human Immunodeficiency Virus Type 1 Reverse Transcriptase and Integrase Interaction written by Shewit Tekeste and published by . This book was released on 2014 with total page 83 pages. Available in PDF, EPUB and Kindle. Book excerpt: Human immunodeficiency virus type 1 (HIV-1) replication requires the reverse transcription of its RNA genome into double-stranded DNA copies within the cytoplasm before integration into the host chromosome. Reverse transcriptase (RT) and integrase (IN) are the viral enzymes responsible for catalyzing the essential steps of reverse transcription and integration, respectively. While numerous studies have led to a greater understanding of the functional roles that RT and IN individually play in HIV-1 replication, little is known about the functional role of RT-IN complex formation in vivo. We hypothesize that RT-IN interaction has functional significance in HIV-1 reverse transcription and replication kinetics. We have mapped the putative binding domain of RT on IN to nine residues on the IN C-terminal domain (CTD). We tested the significance of RT-IN interaction on reverse transcription and viral replication, and identified the step at which viral replication of these IN mutants become defective. We observed impairment of viral cDNA synthesis in viruses harboring IN mutations at the putative RT-binding surface, supporting our hypothesis that the RT-IN interaction during the reverse transcription step is biologically relevant. We have developed a pharmacological approach to study and screen for inhibitors against the RT-IN interaction. Lastly, we have also initiated biochemical studies to determine the IN binding domain domain on RT to contribute to the full understanding of the binding mechanism.

Structure-Based Drug Design

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Publisher : Routledge
ISBN 13 : 1351413058
Total Pages : 668 pages
Book Rating : 4.3/5 (514 download)

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Book Synopsis Structure-Based Drug Design by : Pandi Veerapandian

Download or read book Structure-Based Drug Design written by Pandi Veerapandian and published by Routledge. This book was released on 2018-03-29 with total page 668 pages. Available in PDF, EPUB and Kindle. Book excerpt: Introducing the most recent advances in crystallography, nuclear magnetic resonance, molecular modeling techniques, and computational combinatorial chemistry, this unique, interdisciplinary reference explains the application of three-dimensional structural information in the design of pharmaceutical drugs. Furnishing authoritative analyses by world-renowned experts, Structure-Based Drug Design discusses protein structure-based design in optimizing HIV protease inhibitors and details the biochemical, genetic, and clinical data on HIV-1 reverse transcriptase presents recent results on the high-resolution three-dimensional structure of the catalytic core domain of HIV-1 integrase as a foundation for divergent combination therapy focuses on structure-based design strategies for uncovering receptor antagonists to treat inflammatory diseases demonstrates a systematic approach to the design of inhibitory compounds in cancer treatment reviews current knowledge on the Interleukin-1 (IL-1) system and progress in the development of IL-1 modulators describes the influence of structure-based methods in designing capsid-binding inhibitors for relief of the common cold and much more!

Cumulated Index Medicus

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ISBN 13 :
Total Pages : 1796 pages
Book Rating : 4.3/5 (243 download)

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Book Synopsis Cumulated Index Medicus by :

Download or read book Cumulated Index Medicus written by and published by . This book was released on 2000 with total page 1796 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Unfolding the HIV-1 Reverse Transcriptase RNase H Domain - how to Lose a Molecular Tug-of-war

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ISBN 13 :
Total Pages : 13 pages
Book Rating : 4.:/5 (953 download)

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Book Synopsis Unfolding the HIV-1 Reverse Transcriptase RNase H Domain - how to Lose a Molecular Tug-of-war by :

Download or read book Unfolding the HIV-1 Reverse Transcriptase RNase H Domain - how to Lose a Molecular Tug-of-war written by and published by . This book was released on 2016 with total page 13 pages. Available in PDF, EPUB and Kindle. Book excerpt: Formation of the mature HIV-1 reverse transcriptase (RT) p66/p51 heterodimer requires subunit-specific processing of the p66/p66' homodimer precursor. Since the ribonuclease H (RH) domain contains an occult cleavage site located near its center, cleavage must occur either prior to folding or subsequent to unfolding. Recent NMR studies have identified a slow, subunit-specific RH domain unfolding process proposed to result from a residue tug-of-war between the polymerase and RH domains on the functionally inactive, p66' subunit. Here, we describe a structural comparison of the isolated RH domain with a domain swapped RH dimer that reveals several intrinsically destabilizing characteristics of the isolated domain that facilitate excursions of Tyr427 from its binding pocket and separation of helices B and D. These studies provide independent support for the subunit-selective RH domain unfolding pathway in which instability of the Tyr427 binding pocket facilitates its release followed by domain transfer, acting as a trigger for further RH domain destabilization and subsequent unfolding. As further support for this pathway, NMR studies demonstrate that addition of an RH active site-directed isoquinolone ligand retards the subunit-selective RH' domain unfolding behavior of the p66/p66' homodimer. As a result, this study demonstrates the feasibility of directly targeting RT maturation with therapeutics.

Advances in Metallodrugs

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Publisher : John Wiley & Sons
ISBN 13 : 1119640423
Total Pages : 432 pages
Book Rating : 4.1/5 (196 download)

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Book Synopsis Advances in Metallodrugs by : Shahid Ul-Islam

Download or read book Advances in Metallodrugs written by Shahid Ul-Islam and published by John Wiley & Sons. This book was released on 2020-07-08 with total page 432 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book is organized into 12 important chapters that focus on the progress made by metal-based drugs as anticancer, antibacterial, antiviral, anti-inflammatory, and anti-neurodegenerative agents, as well as highlights the application areas of newly discovered metallodrugs. It can prove beneficial for researchers, investigators and scientists whose work involves inorganic and coordination chemistry, medical science, pharmacy, biotechnology and biomedical engineering.