Induced circular dichroism spectra reveal binding of the antiinflammatory curcumin to human α1-acid glycoprotein
| Autor: | Ferenc Zsila, Miklós Simonyi, Zsolt Bikádi |
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| Rok vydání: | 2004 |
| Předmět: |
Models
Molecular Circular dichroism Curcumin Stereochemistry Clinical Biochemistry Anti-Inflammatory Agents Pharmaceutical Science Plasma protein binding Biochemistry chemistry.chemical_compound Protein structure Drug Discovery Humans Binding site Molecular Biology Binding Sites Molecular Structure Chemistry Circular Dichroism Organic Chemistry Titrimetry Orosomucoid Ligand (biochemistry) Protein tertiary structure Protein Structure Tertiary Spectrometry Fluorescence Docking (molecular) Molecular Medicine Protein Binding |
| Zdroj: | Bioorganic & Medicinal Chemistry. 12:3239-3245 |
| ISSN: | 0968-0896 |
| DOI: | 10.1016/j.bmc.2004.03.074 |
| Popis: | This paper reports the first experimental evidence on binding of the plant derived curcumin molecule to human alpha1-acid glycoprotein (AGP), an acute phase protein in blood. Oppositely signed induced circular dichroism (CD) bands measured in the visible spectral region in pH7.4 phosphate buffer indicate that the protein binds this natural polyphenol molecule in a left-handed chiral conformation. Decreasing of the intrinsic fluorescence of AGP upon addition of curcumin confirmed the binding to take place. Fluorescence quenching titration curve of AGP allowed to calculate the association constant of the ligand (Ka = 4 x 10(4) M(-1)). Modification of near UV CD spectrum of the protein suggests that curcumin induces changes in the tertiary structure of AGP, which leads to the decrease of binding affinity. By using rac-warfarin and amitriptyline, selective high affinity ligands of F1-S and A genetic variants of AGP, CD displacement experiments showed that curcumin is able to bind to both variants. Molecular docking calculations performed on curcumin-AGP and warfarin-AGP complexes suggest the existence of two alternative binding sites for curcumin; either at the open end of the central hydrophobic cavity or in a surface cleft of the protein. |
| Databáze: | OpenAIRE |
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