title: Fibrillogenesis of human serum albumin in the presence of levodopa - spectroscopic, calorimetric and microscopic studies.
abstract: Studying amyloid associated neurodegenerative diseases is an active area of research. Cure for these diseases are still to be discovered. In the present study we have performed comprehensive biophysical and computational experiments showing levodopa not only significantly inhibits heat induced fibrillization of human serum albumin but also disaggregates preformed fibrils. Thioflavin T (ThT) binding assay was used to monitor the fibrillation process of human serum albumin (HSA) at 65°C in the presence and absence of levodopa. Binding of levodopa was studied using isothermal titration calorimetry (ITC), binding constant was found to be 3.6×103M-1. Thermal stabilization effect of levodopa on HSA was studied using differential scanning calorimetry (DSC). Microscopic imaging techniques were employed to analyze the morphology of aggregates and effect of levodopa on aggregation. Further, molecular docking study was also utilized to decipher the amino acid residues involved in the binding interaction of levodopa with HSA. Levodopa interferes in the Fibrillogenesis of HSA by interacting with the amino acid residues near to drug binding site II on the HSA with the binding constant of the order of 103and stabilizes the protein. The results are indicative of the potential use of levodopa as a therapeutic agent for the treatment of amyloid diseases.
authors.affiliation: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh 202002, India.
authors.forename: Mohammad Rehan
authors.initials: MR
authors.lastname: Ajmal
authors.affiliation: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh 202002, India.
authors.forename: Tajalli Ilm
authors.initials: TI
authors.lastname: Chandel
authors.affiliation: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh 202002, India.
authors.forename: Parvez
authors.initials: P
authors.lastname: Alam
authors.affiliation: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh 202002, India.
authors.forename: Nida
authors.initials: N
authors.lastname: Zaidi
authors.affiliation: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh 202002, India.
authors.forename: Masihuz
authors.initials: M
authors.lastname: Zaman
authors.affiliation: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh 202002, India.
authors.forename: Saima
authors.initials: S
authors.lastname: Nusrat
authors.affiliation: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh 202002, India.
authors.forename: Mohsin Vahid
authors.initials: MV
authors.lastname: Khan
authors.affiliation: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh 202002, India.
authors.forename: Mohammad Khursheed
authors.initials: MK
authors.lastname: Siddiqi
authors.affiliation: Molecular Biology Department, Genetic Engineering and Biotechnology Division, National Research Centre, Dokki, Cairo, Egypt.
authors.forename: Yasser E
authors.initials: YE
authors.lastname: Shahein
authors.affiliation: Deanship of Scientific Research, King Saud University, Riyadh, Saudi Arabia; Food Science and Nutrition Department, National Research Center, Dokki, Egypt.
authors.forename: Mohamed H
authors.initials: MH
authors.lastname: Mahmoud
authors.affiliation: Zoology Department, Faculty of Science, Assiut University, 71516 Assiut, Egypt.
authors.forename: Gamal
authors.initials: G
authors.lastname: Badr
authors.affiliation: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh 202002, India. Electronic address: rizwanhkhan1@gmail.com.
authors.forename: Rizwan Hasan
authors.initials: RH
authors.lastname: Khan
mesh_terms: D000682:Amyloid / Q000737:chemistry*; D000978:Antiparkinson Agents / Q000737:chemistry*; D001665:Binding Sites; D002152:Calorimetry, Differential Scanning; D006801:Humans; D007980:Levodopa / Q000737:chemistry*; D062105:Molecular Docking Simulation; D011485:Protein Binding; D055550:Protein Stability; D012709:Serum Albumin / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D000682:Amyloid; D000978:Antiparkinson Agents; D012709:Serum Albumin; D007980:Levodopa
keywords: Human serum albumin; Isothermal titration calorimetry; Levodopa; Molecular docking; Thioflavin T