title: Modulation of the mitochondrial voltage dependent anion channel (VDAC) by curcumin.
abstract: Voltage dependent anion channel (VDAC) of mitochondria plays a crucial role in apoptosis. Human VDAC-1, reconstituted in planar lipid bilayer showed reduced conductance when treated with curcumin. Curcumin interacts with residues in the α helical N-terminus of VDAC and in the channel wall, as revealed by molecular docking, followed by mutational analysis. N-terminus mimicking peptide showed conformational changes in circular dichroism, upon curcumin treatment. We propose that the interaction of curcumin with amino acids in N-terminus and in channel wall fixes the α helix in closed conformation. This restricts its movement which is required for the opening of the channel.
authors.affiliation: Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences Building, Indian Institute of Technology Madras, Chennai 600036, India.
authors.forename: Debanjan
authors.initials: D
authors.lastname: Tewari
authors.affiliation: Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences Building, Indian Institute of Technology Madras, Chennai 600036, India.
authors.forename: Tofayel
authors.initials: T
authors.lastname: Ahmed
authors.affiliation: Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences Building, Indian Institute of Technology Madras, Chennai 600036, India.
authors.forename: Venkat R
authors.initials: VR
authors.lastname: Chirasani
authors.affiliation: Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India.
authors.forename: Pradeep K
authors.initials: PK
authors.lastname: Singh
authors.affiliation: Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India.
authors.forename: Samir K
authors.initials: SK
authors.lastname: Maji
authors.affiliation: Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences Building, Indian Institute of Technology Madras, Chennai 600036, India.
authors.forename: Sanjib
authors.initials: S
authors.lastname: Senapati
authors.affiliation: Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences Building, Indian Institute of Technology Madras, Chennai 600036, India. Electronic address: amal@iitm.ac.in.
authors.forename: Amal Kanti
authors.initials: AK
authors.lastname: Bera
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000235:genetics; D015153:Blotting, Western; D002417:Cattle; D002942:Circular Dichroism; D003474:Curcumin / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D009154:Mutation; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013053:Spectrophotometry; D050995:Voltage-Dependent Anion Channel 1 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D008051:Lipid Bilayers; D024101:Mitochondrial Proteins; C494762:VDAC1 protein, human; D050995:Voltage-Dependent Anion Channel 1; D003474:Curcumin
keywords: Apoptosis; Curcumin; Gating; Ion channel; Mitochondria; VDAC