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Inhibitor and substrate binding induced stability of HIV-1 protease against sequential dissociation and unfolding revealed by high pressure spectroscopy and kinetics

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F70883521%3A28110%2F15%3A43872966" target="_blank" >RIV/70883521:28110/15:43872966 - isvavai.cz</a>

  • Alternative codes found

    RIV/00216208:11310/15:10314758

  • Result on the web

    <a href="http://dx.doi.org/10.1371/journal.pone.0119099" target="_blank" >http://dx.doi.org/10.1371/journal.pone.0119099</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1371/journal.pone.0119099" target="_blank" >10.1371/journal.pone.0119099</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

    Inhibitor and substrate binding induced stability of HIV-1 protease against sequential dissociation and unfolding revealed by high pressure spectroscopy and kinetics

  • Original language description

    High-pressure methods have become an interesting tool of investigation of structural stability of proteins. They are used to study protein unfolding, but dissociation of oligomeric proteins can be addressed this way, too. HIV-1 protease, although an interesting object of biophysical experiments, has not been studied at high pressure yet. In this study HIV-1 protease is investigated by high pressure (up to 600 MPa) fluorescence spectroscopy of either the inherent tryptophan residues or external 8-anilino-1-naphtalenesulfonic acid at 25oC. A fast concentration-dependent structural transition is detected that corresponds to the dimer-monomer equilibrium. This transition is followed by a slow concentration independent transition that can be assigned to the monomer unfolding. In the presence of a tight-binding inhibitor none of these transitions are observed, which confirms the stabilizing effect of inhibitor. High-pressure enzyme kinetics (up to 350 MPa) also reveals the stabilizing effect of substrate. Unfolding of the protease can thus proceed only from the monomeric state after dimer dissociation and is unfavourable at atmospheric pressure. Dimer-destabilizing effect of high pressure is caused by negative volume change of dimer dissociation of -32.5 mL/mol. It helps us to determine the atmospheric pressure dimerization constant of 0.92 μM. High-pressure methods thus enable the investigation of structural phenomena that are difficult or impossible to measure at atmospheric pressure.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

  • CEP classification

    CE - Biochemistry

  • OECD FORD branch

Result continuities

  • Project

    <a href="/en/project/GBP208%2F12%2FG016" target="_blank" >GBP208/12/G016: Controlling structure and function of biomolecules at the molecular scale: theory meets experiment</a><br>

  • Continuities

    V - Vyzkumna aktivita podporovana z jinych verejnych zdroju

Others

  • Publication year

    2015

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Data specific for result type

  • Name of the periodical

    PLoS ONE

  • ISSN

    1932-6203

  • e-ISSN

  • Volume of the periodical

    10

  • Issue of the periodical within the volume

    3

  • Country of publishing house

    US - UNITED STATES

  • Number of pages

    27

  • Pages from-to

    "@@@###"

  • UT code for WoS article

    000351284600050

  • EID of the result in the Scopus database