Structure of HIV-1 protease in complex with potent inhibitor KNI-272 determined by high-resolution X-ray and neutron crystallography

No abstract is available for this paper.

• Publication year

  2009

• Venue

  Proceedings of the National Academy of Sciences of the United States of America

• Publication date

  2009-03-24

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1073/pnas.0809400106PMID 19273847PMCID PMC2660780
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Reprint of "Crystal structure of chemically synthesized HIV-1 protease and a ketomethylene isostere inhibitor based on the p2/NC cleavage site" [Bioorg. Med. Chem. Lett. 18 (2008) 4554-4557].

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• Crystallization and preliminary neutron diffraction studies of HIV-1 protease cocrystallized with inhibitor KNI-272.

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• Design of HIV protease inhibitors targeting protein backbone: an effective strategy for combating drug resistance.

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• The catalytic mechanism of an aspartic proteinase explored with neutron and X-ray diffraction.

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• Crystal structure of chemically synthesized HIV-1 protease and a ketomethylene isostere inhibitor based on the p2/NC cleavage site.

  2008cited by this paper
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• Binding free energy contributions of interfacial waters in HIV-1 protease/inhibitor complexes.

  2006cited by this paper
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  2006cited by this paper
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  2006cited by this paper
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  2006cited by this paper
• Catalysis and linear free energy relationships in aspartic proteases.

  2006cited by this paper
• Observation of a tetrahedral reaction intermediate in the HIV-1 protease-substrate complex.

  2005cited by this paper
• Prospects for atomic resolution and neutron crystallography in drug design.

  2004cited by this paper
• A new neutron single-crystal diffractometer dedicated for biological macromolecules (BIX-4).

  2004cited by this paper
• The role of hydrogen bonding in the enzymatic reaction catalyzed by HIV‐1 protease

  2004cited by this paper
• HIV-1 protease: mechanism and drug discovery.

  2003cited by this paper
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  2003cited by this paper
• Caught in the act: alpha-synuclein is the culprit in Parkinson's disease.

  2003cited by this paper
• [AIDS--the first 20 years].

  2001cited by this paper
• AIDS--the first 20 years.

  2001cited by this paper
• Ab initio molecular dynamics-based assignment of the protonation state of pepstatin A/HIV-1 protease cleavage site.

  2001cited by this paper
• Follow the protons: a low-barrier hydrogen bond unifies the mechanisms of the aspartic proteases.

  2001cited by this paper
• Thermodynamic dissection of the binding energetics of KNI‐272, a potent HIV‐1 protease inhibitor

  2000cited by this paper
• Small dipeptide-based HIV protease inhibitors containing the hydroxymethylcarbonyl isostere as an ideal transition-state mimic.

  1999cited by this paper
• Crystallography & NMR system: A new software suite for macromolecular structure determination.

  1998influential reference
• Inhibitors of HIV-1 protease: a major success of structure-assisted drug design.

  1998cited by this paper
• SHELXL: high-resolution refinement.

  1997cited by this paper
• Processing of X-ray diffraction data collected in oscillation mode.

  1997cited by this paper
• [20] Processing of X-ray diffraction data collected in oscillation mode.

  1997cited by this paper
• Ionization states of the catalytic residues in HIV-1 protease

  1996influential reference
• Inhibition and catalytic mechanism of HIV-1 aspartic protease.

  1996cited by this paper
• Design and synthesis of substrate-based peptidomimetic human immunodeficiency virus protease inhibitors containing the hydroxymethylcarbonyl isostere.

  1996cited by this paper
• Solution NMR evidence that the HIV-1 protease catalytic aspartyl groups have different ionization states in the complex formed with the asymmetric drug KNI-272.

  1996cited by this paper
• Bound Water Molecules at the Interface between the HIV-1 Protease and a Potent Inhibitor, KNI-272, Determined by NMR

  1996cited by this paper
• Structure of HIV-1 protease with KNI-272, a tight-binding transition-state analog containing allophenylnorstatine.

  1995cited by this paper
• Viral dynamics in human immunodeficiency virus type 1 infection

  1995cited by this paper
• A low-barrier hydrogen bond in the catalytic triad of serine proteases.

  1994cited by this paper
• The HIV-1 protease as enzyme and substrate: mutagenesis of autolysis sites and generation of a stable mutant with retained kinetic properties.

  1994cited by this paper
• Rational design of potent, bioavailable, nonpeptide cyclic ureas as HIV protease inhibitors.

  1994cited by this paper
• Low-barrier hydrogen bonds and enzymic catalysis.

  1994cited by this paper
• Retroviral reverse transcriptases: error frequencies and mutagenesis.

  1992cited by this paper
• Kynostatin (KNI)-227 and -272, highly potent anti-HIV agents: conformationally constrained tripeptide inhibitors of HIV protease containing allophenylnorstatine.

  1992cited by this paper
• A visual protein crystallographic software system for X11/Xview

  1992influential reference
• Human immunodeficiency virus-1 protease. 1. Initial velocity studies and kinetic characterization of reaction intermediates by 18O isotope exchange.

  1991cited by this paper
• Active human immunodeficiency virus protease is required for viral infectivity.

  1988cited by this paper
• An 11-kDa form of human immunodeficiency virus protease expressed in Escherichia coli is sufficient for enzymatic activity.

  1988cited by this paper
• Human immunodeficiency virus protease expressed in Escherichia coli exhibits autoprocessing and specific maturation of the gag precursor.

  1987cited by this paper
• A procedure for joint refinement of macromolecular structures with X‐ray and neutron diffraction data from single crystals

  1982cited by this paper
• Electronic Reprint Biological Crystallography Phenix: Building New Software for Automated Crystallographic Structure Determination Biological Crystallography Phenix: Building New Software for Automated Crystallographic Structure Determination

  year unknowninfluential reference

• Integrated Boltzmann Sampling: A Few-State Approach for Efficient Multistate Free Energy Calculations.

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  2024cites this paper
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• Leveraging a Separation of States Method for Relative Binding Free Energy Calculations in Systems with Trapped Waters

  2024cites this paper
• WaterKit: Thermodynamic Profiling of Protein Hydration Sites.

  2023cites this paper
• Non-Canonical Amino Acids in Analyses of Protease Structure and Function

  2023cites this paper
• Comprehending the Structure, Dynamics, and Mechanism of Action of Drug-Resistant HIV Protease

  2023cites this paper
• Newly identified C-H⋯O hydrogen bond in histidine.

  2022cites this paper
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  2022cites this paper
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• System truncation accelerates binding affinity calculations with the fragment molecular orbital method: A benchmark study

  2022cites this paper
• The reorganization energy of compounds upon binding to proteins, from dynamic and solvated bound and unbound states.

  2021cites this paper
• Decoding the Structure of Non-Proteinogenic Amino Acids: The Rotational Spectrum of Jet-Cooled Laser-Ablated Thioproline

  2021influential citation
• Hybrid QM/MM Free-Energy Evaluation of Drug-Resistant Mutational Effect on the Binding of an Inhibitor Indinavir to HIV-1 Protease

  2021cites this paper
• Enzymes as Drug Targets

  2021cites this paper
• Combining Molecular Dynamic Information and an Aspherical-Atom Data Bank in the Evaluation of the Electrostatic Interaction Energy in Multimeric Protein-Ligand Complex: A Case Study for HIV-1 Protease

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  2020cites this paper
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  2020cites this paper
• Therapeutic approaches against coronaviruses acute respiratory syndrome

  2020cites this paper
• The role of hydrogen atoms in redox catalysis by the flavoenzyme cholesterol oxidase.

  2020cites this paper
• Complementary Information from Neutron Crystallography Studies

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  2020cites this paper
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  2019cites this paper
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  2018cites this paper
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  2018cites this paper
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  2018cites this paper
• Neutron macromolecular crystallography.

  2018cites this paper
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  2017cites this paper
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