title: Underlying molecular interaction of bovine serum albumin and linezolid: a biophysical outlook.
abstract: Linezolid, one of the reserve antibiotic of oxazolidinone class has wide range of antimicrobial activity. Here we have conducted a fundamental study concerning the dynamics of its interaction with bovine serum albumin (BSA), and the post binding modification of the later by employing different spectroscopic (absorption, fluorescence and circular dichroism (CD) spectroscopy) and molecular docking tools. Gradual quenching of the tryptophan (Trp) fluorescence upon addition of linezolid to BSA confirms their interaction. Analysis of fluorescence quenching at different temperature indicates that the interaction is made by static complex formation and the BSA has one binding site for the drug. The negative Gibbs energy change (ΔG0), and positive values of enthalpy change (ΔH0) and entropy change (ΔS0) strongly suggest that it is an entropy driven spontaneous and endothermic reaction. The reaction involves hydrophobic pocket of the protein, which is further stabilized by hydrogen bonding and electrostatic interactions as evidenced from 8-anilino-1-napthalene sulfonic acid, sucrose and NaCl binding studies. These findings also support the molecular docking study using AutoDock 4.2. The influence of this interaction on the secondary structure of the protein is negligible as evidenced by CD spectroscopy. So, from these findings, we conclude that linezolid interacts with BSA in 1:1 ratio through hydrophobic, hydrogen bonding and ionic interactions, and this may not affect the secondary structure of the protein.
authors.affiliation: a Department of Physiology , University Colleges of Science and Technology, University of Calcutta , 92, A.P.C. Road, Kolkata 700 009 , India.
authors.forename: Amartya
authors.initials: A
authors.lastname: Roy
authors.affiliation: a Department of Physiology , University Colleges of Science and Technology, University of Calcutta , 92, A.P.C. Road, Kolkata 700 009 , India.
authors.forename: Paromita
authors.initials: P
authors.lastname: Seal
authors.affiliation: a Department of Physiology , University Colleges of Science and Technology, University of Calcutta , 92, A.P.C. Road, Kolkata 700 009 , India.
authors.forename: Jyotirmoy
authors.initials: J
authors.lastname: Sikdar
authors.affiliation: a Department of Physiology , University Colleges of Science and Technology, University of Calcutta , 92, A.P.C. Road, Kolkata 700 009 , India.
authors.forename: Sanghamitra
authors.initials: S
authors.lastname: Banerjee
authors.affiliation: a Department of Physiology , University Colleges of Science and Technology, University of Calcutta , 92, A.P.C. Road, Kolkata 700 009 , India.
authors.forename: Rajen
authors.initials: R
authors.lastname: Haldar
mesh_terms: D000818:Animals; D001665:Binding Sites; D002417:Cattle; D002942:Circular Dichroism; D006860:Hydrogen Bonding / Q000187:drug effects; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D000069349:Linezolid / Q000737:chemistry* / Q000494:pharmacology; D062105:Molecular Docking Simulation; D011485:Protein Binding / Q000187:drug effects*; D017433:Protein Structure, Secondary / Q000187:drug effects; D012710:Serum Albumin, Bovine / Q000737:chemistry*; D013050:Spectrometry, Fluorescence; D017550:Spectroscopy, Fourier Transform Infrared; D013816:Thermodynamics
chemical_list: D012710:Serum Albumin, Bovine; D000069349:Linezolid
keywords: BSA; linezolid; molecular docking; spectroscopy