TY - JOUR
T1 - Molecular interactions of cefoperazone with bovine serum albumin
T2 - Extensive experimental and computational investigations
AU - Ali, Mohd Sajid
AU - Muthukumaran, Jayaraman
AU - Jain, Monika
AU - Santos-Silva, Teresa
AU - Al-Lohedan, Hamad A.
AU - Al-Shuail, Noura Saad
N1 - Funding Information:
The authors are grateful to the Deanship of Scientific Research, King Saud University, for funding through the Vice Deanship of Scientific Research Chairs.
info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID%2FMulti%2F04378%2F2019/PT#
info:eu-repo/grantAgreement/FCT/OE/SFRH%2FBPD%2F97719%2F2013/PT#
Funding Information:
The authors are grateful to the Deanship of Scientific Research, King Saud University, for funding through the Vice Deanship of Scientific Research Chairs. JM and TSS thanks to Prof. Maria Jo?o Rom?o (UCIBIO-NOVA, FCT-UNL) for her support during this work. The computational work was supported by the Applied Molecular Biosciences Unit-UCIBIO.
Publisher Copyright:
© 2021 Elsevier B.V.
PY - 2021/9/1
Y1 - 2021/9/1
N2 - We investigated the binding of the cephalosporin-class drug cefoperazone (CFP) with bovine serum albumin (BSA) using spectroscopic techniques and in silico methods. The aim of this study was to (i) emphasize the importance of correcting for the inner filter effect in this type of study and (ii) understand the binding mechanism of CFP with BSA by addressing protein conformation and plausible binding sites. Formation of the complex was confirmed by UV–visible spectroscopy. Quenching of BSA fluorescence in the presence of CFP was also observed. Because of the high absorption of CFP in the fluorescence emission range of BSA, the fluorescence emission spectra were corrected for the inner filter effect. Fluorescence emission was studied at excitation wavelengths of 280 and 295 nm. The uncorrected data showed a significant contribution of tyrosine at the excitation wavelength of 280 nm; however, after correction, this contribution became negligible. The static-type mechanism was found to be involved in quenching, with almost 1:1 binding between BSA and CFP. Hydrogen bonding and hydrophobic forces were found to dominate the protein–ligand interactions with a slight decrease in the α-helical contents. Synchronous fluorescence spectral data (at Δλ = 15 and 60 nm) were also corrected for the inner filter effect, with the results being similar to those of excitation at 280 and 295 nm. Molecular docking and molecular dynamics (MD) simulation results suggest that, apart from the two known drug binding sites (drug site I and II), one putative binding site (binding site III) located between BSA domains 1 and 3 was also possible for CFP. MD simulations of the previously reported drug binding sites (drug site I and II) and putative binding site III revealed that binding site III showed excellent binding profiles and could be a target for future research related to BSA-drug binding.
AB - We investigated the binding of the cephalosporin-class drug cefoperazone (CFP) with bovine serum albumin (BSA) using spectroscopic techniques and in silico methods. The aim of this study was to (i) emphasize the importance of correcting for the inner filter effect in this type of study and (ii) understand the binding mechanism of CFP with BSA by addressing protein conformation and plausible binding sites. Formation of the complex was confirmed by UV–visible spectroscopy. Quenching of BSA fluorescence in the presence of CFP was also observed. Because of the high absorption of CFP in the fluorescence emission range of BSA, the fluorescence emission spectra were corrected for the inner filter effect. Fluorescence emission was studied at excitation wavelengths of 280 and 295 nm. The uncorrected data showed a significant contribution of tyrosine at the excitation wavelength of 280 nm; however, after correction, this contribution became negligible. The static-type mechanism was found to be involved in quenching, with almost 1:1 binding between BSA and CFP. Hydrogen bonding and hydrophobic forces were found to dominate the protein–ligand interactions with a slight decrease in the α-helical contents. Synchronous fluorescence spectral data (at Δλ = 15 and 60 nm) were also corrected for the inner filter effect, with the results being similar to those of excitation at 280 and 295 nm. Molecular docking and molecular dynamics (MD) simulation results suggest that, apart from the two known drug binding sites (drug site I and II), one putative binding site (binding site III) located between BSA domains 1 and 3 was also possible for CFP. MD simulations of the previously reported drug binding sites (drug site I and II) and putative binding site III revealed that binding site III showed excellent binding profiles and could be a target for future research related to BSA-drug binding.
KW - Albumin binding
KW - Cefoperazone
KW - Inner filter effect
KW - Molecular docking
KW - Molecular dynamics
UR - http://www.scopus.com/inward/record.url?scp=85105878738&partnerID=8YFLogxK
U2 - 10.1016/j.molliq.2021.116354
DO - 10.1016/j.molliq.2021.116354
M3 - Article
AN - SCOPUS:85105878738
SN - 0167-7322
VL - 337
JO - Journal of Molecular Liquids
JF - Journal of Molecular Liquids
M1 - 116354
ER -