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Conference: Bucharest University Faculty of Physics 2010 Meeting

Section: Biophysics and Medical Physics;Electricity and Magnetism

Title:

Analysis of MD Simulation for L58H Mutant of Human Transthyretin

Authors:

Marian Butu (1),(2), Alina Butu (1)

Affiliation:

(1) National Institute of Research and Development for Biological Sciences, Splaiul Independentei 296 sector 6 Bucharest, Romania

(2) Faculty of Physics, University of Bucharest, Str. Atomistilor 405, Bucharest-Magurele, Romania

E-mail

marian_butu@yahoo.com

Keywords:

human transthyretin, point mutation, molecular dynamics simulation

Abstract:

Transthyretin is a protein found in human blood and cerebrospinal fluid and it is involved in the transport of thyroid hormones. Dissociation of the transthyretin tetramer into monomers, which misfold and forming amyloid deposits in various organs is cause of amyloid diseases. The formation of amyloid fibrils from human TTR is known to be triggered by acidic pH. L58H is a point mutant of human transthyretin (TTR). To study conformational changes preceding the formation of amyloid it was analyzed the L58H mutant forms at pH 7.5 and 4.6 by molecular dynamics simulation method. The trajectories with a length of 10ns were analyzed with GROMACS software package. Start coordinates were the structures 3DJR and 3DJS from Protein Data Bank determinate by X-ray diffraction. It were analyzed the structural and dynamic properties - RMS, accessibility surface area, dihedrals, distances between Cα atoms. Acknowledgments: This work was supported by the PNCDI II - P4 Partnerships research contract no 62-056/2008. References: 1. Miyata, M., Sato, T., Mizuguchi, M., Nakamura, T., Ikemizu, S., Nabeshima, Y., Susuki, S., Suwa, Y., Morioka, H., Ando, Y., Suico, M.A., Shuto, T., Koga, T., Yamagata, Y., Kai, H., (2010) Role of the Glutamic Acid 54 Residue in Transthyretin Stability and Thyroxine Binding, Biochemistry; 49(1):114-23 2. Pasquato, N., Berni, R., Folli, C., Alfieri, B., Cendron, L., Zanotti, G. (2007) Acidic pH-induced conformational changes in amyloidogenic mutant transthyretin. J.Mol.Biol. 366: 711-719 3. Prapunpoj P, Leelawatwattana L., (2009) Evolutionary changes to transthyretin: structure-function relationships. FEBS J., 276(19):5330-41