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Influence of ligand binding on structure and thermostability of human alpha(1)-acid glycoprotein

Result description

Ligand binding of neutral progesterone, basic propranolol, and acidic warfarin to human alpha(1)-acid glycoprotein (AGP) was investigated by Raman spectroscopy. The binding itself is characterized by a uniform conformational shift in which a tryptophan residue is involved. Slight differences corresponding to different contacts of the individual ligands inside the beta-barrel are described. Results are compared with in silico ligand docking into the available crystal structure of deglycosylated AGP using quantum/molecular mechanics. Calculated binding energies are -18.2, -14.5, and -11.5 kcal/mol for warfarin, propranolol, and progesterone, respectively. These calculations are consistent with Raman difference spectroscopy; nevertheless, minor discrepancies in the precise positions of the ligands point to structural differences between deglycosylated and native AGP.

Keywords

orosomucoidbinding siteRaman spectroscopy

The result's identifiers

Alternative languages

  • Result language

    angličtina

  • Original language name

    Influence of ligand binding on structure and thermostability of human alpha(1)-acid glycoprotein

  • Original language description

    Ligand binding of neutral progesterone, basic propranolol, and acidic warfarin to human alpha(1)-acid glycoprotein (AGP) was investigated by Raman spectroscopy. The binding itself is characterized by a uniform conformational shift in which a tryptophan residue is involved. Slight differences corresponding to different contacts of the individual ligands inside the beta-barrel are described. Results are compared with in silico ligand docking into the available crystal structure of deglycosylated AGP using quantum/molecular mechanics. Calculated binding energies are -18.2, -14.5, and -11.5 kcal/mol for warfarin, propranolol, and progesterone, respectively. These calculations are consistent with Raman difference spectroscopy; nevertheless, minor discrepancies in the precise positions of the ligands point to structural differences between deglycosylated and native AGP.

  • Czech name

  • Czech description

Classification

  • Type

    Jx - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

  • CEP classification

    CE - Biochemistry

  • OECD FORD branch

Result continuities

  • Project

  • Continuities

    I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Others

  • Publication year

    2016

  • Confidentiality

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

Data specific for result type

  • Name of the periodical

    Journal of Molecular Recognition

  • ISSN

    0952-3499

  • e-ISSN

  • Volume of the periodical

    29

  • Issue of the periodical within the volume

    2

  • Country of publishing house

    US - UNITED STATES

  • Number of pages

    10

  • Pages from-to

    70-79

  • UT code for WoS article

    000368640400002

  • EID of the result in the Scopus database

    2-s2.0-84955666818