Organogold complexes probe a large β-barrel cavity for human serum α1-acid glycoprotein

Ferenc Zsila, Zsolt Bikádi, Eszter Hazai, Ágnes Simon, Ilona Fitos, György Mády

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Human α1-acid glycoprotein (AAG) is an acute phase component of the plasma, binding numerous drugs and natural compounds with high-affinity. Using circular dichroism (CD) spectroscopy, strong AAG binding of organogold complexes was found, the molecular size and chemical structure of which differ from known AAG binding agents. The 16-membered Au2P4C8O2 macrocycles interconvert rapidly between two helical forms and produce enantiomeric conformations which are in dynamic equilibrium in solution. AAG binds preferentially one of the chiral conformers as indicated by strong Cotton effects generated by intramolecular exciton coupling between the pairs of hetercyclic chromophores. Lipophilic nature of the guest molecules suggests the dominant contribution of hydrophobic interactions in the AAG binding. Comparison of the main genetic variants of AAG revealed that both the 'F1/S' and 'A' variants bind with high-affinity the gold(I) macrocycles (Ka ≈ 106 M- 1). CD/fluorescence displacement, and fluorescence quenching experiments indicated inclusion of the compounds into the central β-barrel cavity of AAG of which exact tertiary structure is yet unknown. Molecular dimensions of the gold(I) macrocycles (13 × 14 × 14 Å) indicate that the principal ligand binding cavity of both the 'F1/S' and 'A' variants must be larger compared to the models published to date. Based on these findings, a novel homology model of AAG 'F1' variant was constructed using the human neutrophil gelatinase-associated lipocalin as a template. The organogold complexes were successfully docked into the central cavity of this model.

Original languageEnglish
Pages (from-to)1106-1114
Number of pages9
JournalBiochimica et Biophysica Acta - Proteins and Proteomics
Volume1784
Issue number7-8
DOIs
Publication statusPublished - Jul 2008

Fingerprint

Circular Dichroism
Gold
Glycoproteins
Fluorescence
Acids
Serum
Hydrophobic and Hydrophilic Interactions
Circular dichroism spectroscopy
Lipocalins
Gelatinases
Spectrum Analysis
Chromophores
Ligands
Cotton
Conformations
Quenching
Pharmaceutical Preparations
Plasmas
Molecules
Experiments

Keywords

  • Chiral conformational interconversion
  • Human serum α-acid glycoprotein
  • Induced circular dichroism
  • Molecular modelling
  • Organogold complexes

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Genetics

Cite this

Organogold complexes probe a large β-barrel cavity for human serum α1-acid glycoprotein. / Zsila, Ferenc; Bikádi, Zsolt; Hazai, Eszter; Simon, Ágnes; Fitos, Ilona; Mády, György.

In: Biochimica et Biophysica Acta - Proteins and Proteomics, Vol. 1784, No. 7-8, 07.2008, p. 1106-1114.

Research output: Contribution to journalArticle

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