Structure Function Studies Of Hiv 1 Protease
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Structure Function Studies Of Hiv 1 Protease
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Author : Bradley James Keusch
language : en
Publisher:
Release Date : 2016
Structure Function Studies Of Hiv 1 Protease written by Bradley James Keusch and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2016 with Biochemistry categories.
HIV-1 is the causative agent of the devastating human disease Acquired Immunodeficiency Syndome (AIDS). While much progress has been made over the past two decades, HIV-1 remains a major global health concern. HIV-1 protease is 99-amino acid homodimer aspartyl protease that is essential to the life cycle of HIV. This has rendered it an attractive and very successful drug target. However, due to the high error rate of the HIV -1 reverse transcriptase, drug resistance mutations in the protease can develop very rapidly in some patients, rendering current protease inhibitors (one of the main classes of drug in common antiretroviral therapy) less effective or completely ineffective. In this thesis, we investigate the structural impact of a number of HIV-1 protease drug resistance mutations. These include L33F, which is selected for on darunavir treatment (one of the most prescirbed protease inhibitors), I47V, and V54I (which we identify as compensatory mutations involved in the tethering of the protease flaps and proper formation of the active site). A fuller understanding of the structural impact of these resistance mutations will hopefully facilitate the development of protease inhibitors that can overcome this common drug resistance.
Probing Structure Function Relationships In Hiv 1 Protease Via Molecular Dynamic Simulations
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Author : William Edward Harte
language : en
Publisher:
Release Date : 1992
Probing Structure Function Relationships In Hiv 1 Protease Via Molecular Dynamic Simulations written by William Edward Harte and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 1992 with HIV (Viruses) categories.
Structure Function Studies Of Hiv 1 Reverse Transcriptase
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Author : Seddon Y. Thomas
language : en
Publisher:
Release Date : 1996
Structure Function Studies Of Hiv 1 Reverse Transcriptase written by Seddon Y. Thomas and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 1996 with HIV (Viruses) categories.
Structure Function Studies Of Hiv 1 Reverse Transcriptase
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Author : Justin Cole
language : en
Publisher:
Release Date : 1996
Structure Function Studies Of Hiv 1 Reverse Transcriptase written by Justin Cole and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 1996 with HIV (Viruses) categories.
Viral Proteases And Their Inhibitors
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Author : Satya Prakash Gupta
language : en
Publisher: Academic Press
Release Date : 2017-07-03
Viral Proteases And Their Inhibitors written by Satya Prakash Gupta and has been published by Academic Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2017-07-03 with Science categories.
Viral Proteases and Their Inhibitors provides a thorough examination of viral proteases from their molecular components, to therapeutic applications. As information on three dimensional structures and biological functions of these viral proteases become known, unexpected protein folds and unique mechanisms of proteolysis are realized. This book investigates how this facilitates the design and development of potent antiviral agents used against life-threatening viruses. Users will find descriptions of each virus that detail the structure and function of viral proteases, discuss the design and development of inhibitors, and analyze the structure-activity relationships of inhibitors. This book is ideal biochemists, virologists and those working on antiviral agents. Provides comprehensive, state-of-the-art coverage of virus infections, the virus lifecycle, and mechanisms of protease inhibition Analyzes structure-activity relationships of inhibitors of each viral protease Presents an in-depth view of the structure and function of viral proteases
Probing The Mechanism Of Hiv 1 Protease Through Total Chemical Synthesis
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Author : Manuel Baca
language : en
Publisher:
Release Date : 1994
Probing The Mechanism Of Hiv 1 Protease Through Total Chemical Synthesis written by Manuel Baca and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 1994 with HIV (Viruses) categories.
Total chemical synthesis has been used to explore structure-function relationships of the protease from human immunodeficiency virus 1 (HIV-1 protease). Analogues of this enzyme were prepared by conventional stepwise solid phase peptide synthesis and by chemical ligation of unprotected peptide segments. These analogues contained unnatural elements of structure, each designed to address a specific aspect of HIV-1 protease structure-function. Replacement of a surface [beta]-turn in each subunit of the homodimeric enzyme with a constrained, type II [prime] [beta]-turn mimic produced a fully active enzyme analogue with enhanced resistance to thermal inactivation. These results indicate that the precise geometry of this [beta]-turn is not critical for activity, and that replacement of native sequence with a rigid [beta]-turn mimic can lead to superior protein stability. Mass spectrometric and NMR experiments were designed to study the properties of a solution enzyme-inhibitor complex. No evidence for a specifically bound water molecule was found in the noncovalent ternary complex between the homodimeric enzyme and a reversible substrate-based inhibitor as detected by mass spectrometry. Bound water is reputedly involved in mediating hydrogen bonds between the enzyme flaps and substrate P2 and P1 [prime] carbonyls. The mode of binding and catalytic contribution of these enzyme-substrate hydrogen bonds was also investigated. An analogue of HIV-1 protease was designed in which the functionally relevant amide -CONH- linkage between residues Gly[49]-Ile[50] in each flap was replaced by an isosteric thioester -COS- bond. The catalytic activity (kcat) of the backbone modified enzyme was reduced approximately 3000 fold compared to the native amide bond-containing enzyme. This result confirms that backbone hydrogen bonds from the enzyme flaps to substrate are important for the catalytic function of the HIV-1 protease. These hydrogen bonds were further studied by removing the hydrogen bonding potential from one flap only. Existing peptide ligation methods were adapted to allow the linking of multiple peptide segments. Using these new methods, a tethered dimer analogue of HIV-1 protease was prepared in which the Gly[49]-Ile[50] amide bond was replaced in one subunit only by an ester -COO- bond. The kcat for this tethered dimer analogue was reduced only twofold. This suggests that both flap-substrate hydrogen bonds may originate from only a single flap, and not symmetrically from each flap as has been observed crystallographically. This hydrogen bonding pattern would coincide with that observed for the related pepsin-like aspartic proteases. Elucidation of the mechanistically relevant pattern of enzyme-substrate hydrogen bonding could have important applications to the design of HIV-1 protease inhibitors.
Overexpression And Structure Function Characterization Of Hiv 1 Subtype C Reverse Transcriptase And Protease
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Author :
language : en
Publisher:
Release Date : 2019
Overexpression And Structure Function Characterization Of Hiv 1 Subtype C Reverse Transcriptase And Protease written by and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2019 with AIDS (Desease) categories.
Structure Function Studies Of Virus Protein R From Human Immunodeficiency Virus 1
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Author : Sabine C. Piller
language : en
Publisher:
Release Date : 1998
Structure Function Studies Of Virus Protein R From Human Immunodeficiency Virus 1 written by Sabine C. Piller and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 1998 with AIDS (Disease) categories.
Handbook Of Antimicrobial Resistance
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Author : Matthias Gotte
language : en
Publisher: Springer
Release Date : 2018-02-12
Handbook Of Antimicrobial Resistance written by Matthias Gotte and has been published by Springer this book supported file pdf, txt, epub, kindle and other format this book has been release on 2018-02-12 with Medical categories.
While many volumes have been written about various aspects of antimicrobial resistance, this book is a comprehensive reference work. All manifestations of resistance are addressed: viral; bacterial, parasitical and fungal are given dedicated sections. The underlining molecular mechanisms, which depend not only on the microbe but on the specific drug (target), are highly diverse. This work discusses and compares the biological, biochemical and structural aspects of resistance and its evolution.
Hiv 1 Integrase
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Author : Nouri Neamati
language : en
Publisher: John Wiley & Sons
Release Date : 2011-08-10
Hiv 1 Integrase written by Nouri Neamati and has been published by John Wiley & Sons this book supported file pdf, txt, epub, kindle and other format this book has been release on 2011-08-10 with Science categories.
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.