Asngari, Nurul Jannah Mohd and Bakar, Khairul Azreena and Feroz, Shevin Rizal and Razak, Fathilah Abdul and Abd Halim, Adyani Azizah (2024) Interaction mechanism of a cysteine protease inhibitor, odanacatib, with human serum albumin: In vitro and bioinformatics studies. BIOPHYSICAL CHEMISTRY, 305. ISSN 1873-4200, DOI https://doi.org/10.1016/j.bpc.2023.107140.
Full text not available from this repository.Abstract
Odanacatib (ODN) is a selective cathepsin K inhibitor that acts as an anti-resorptive agent to treat osteoporosis. ODN is also found effective in reducing the effect of severe periodontitis. The interaction between ODN and human serum albumin (HSA) was investigated using spectroscopic, microscopic, and in silico approaches to characterize their binding. The fluorescence intensity of HSA increased upon the addition of increasing concentrations of ODN accompanied by blueshift in the fluorescence spectrum, which suggested hydrophobic formation around the microenvironment of the fluorophores upon ODN binding. A moderate binding affinity was obtained for ODN-HSA binding, with binding constant (K-a) values of similar to 10(4) M-1. Circular dichroism results suggested that the overall secondary and tertiary structures of HSA were both only slightly altered upon ODN binding. The surface morphology of HSA was also affected upon ODN binding, showing aggregate formation. Drug displacement and molecular docking results revealed that ODN preferably binds to site III in subdomain IB of HSA, while molecular dynamics simulations indicated formation of a stable protein complex when site III was occupied by ODN. The ODN-HSA complex was mainly stabilized by a combination of hydrogen bonding, hydrophobic interactions, and van der Waals forces. These findings provide additional information to understand the interaction mechanism of ODN in blood circulation and may help in future improvements on the adverse effects of ODN.
| Item Type: | Article |
|---|---|
| Funders: | Universiti Malaya Faculty Research Grant [GPF006E-2018] |
| Uncontrolled Keywords: | Drug-protein binding; Fluorescence spectroscopy; Human serum albumin; Molecular docking; Odanacatib |
| Subjects: | R Medicine > RK Dentistry |
| Divisions: | Faculty of Dentistry |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 11 Jun 2024 07:01 |
| Last Modified: | 11 Jun 2024 07:01 |
| URI: | http://eprints.um.edu.my/id/eprint/44156 |
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