TAILIEUCHUNG - Báo cáo khoa học: Data-driven homology modelling of P-glycoprotein in the ATP-bound state indicates flexibility of the transmembrane domains

H2O2 induces apoptosis in variety of cells; however, the sensitivities of testicular germ cells to H2O2are not known. In the present study, H2O2 ,at concentrations in the range 1–10lm, was found to induce apoptosis in testicular germ cells in vitro. | Data-driven homology modelling of P-glycoprotein in the ATP-bound state indicates flexibility of the transmembrane domains Thomas Stockner1 Sjoerd J. de Vries2 Alexandre M. J. J. Bonvin2 Gerhard F. Ecker3 and Peter Chiba4 1 Bioresources Austrian Research Centers GmbH - ARC Seibersdorf Austria 2 NMR Research Group Bijvoet Center for Biomolecular Research Utrecht University The Netherlands 3 Emering Field Pharmacoinformatics University of Vienna Austria 4 Institute of MedicalChemistry MedicalUniversity of Vienna Austria Keywords ABC transporter ATP-bound P-gp model cysteine cross-links data-driven homology modelling P-glycoprotein Correspondence T. Stockner Bioresources Austrian Research Centers GmbH - ARC 2444 Seibersdorf Austria Fax 43 050550 3520 Tel 43 050550 3588 E-mail Website http Database The coordinates of the data-driven crosslinked model are available at the Protein ModelDatabase http PMDB PMDB ID PM0075213 Human P-glycoprotein is an ATP-binding cassette transporter that plays an important role in the defence against potentially harmful molecules from the environment. It is involved in conferring resistance against cancer therapeutics and plays an important role for the pharmacokinetics of drugs. The lack of a high resolution structure of P-glycoprotein has hindered its functional understanding and represents an obstacle for structure based drug development. The homologous bacterial exporter Sav1866 has been shown to share a common architecture and overlapping substrate specificity with P-glycoprotein. The structure of Sav1866 suggests that helices in the transmembrane domains diverge at the extracytoplasmic face whereas cross-link information and a combination of small angle X-ray scattering and cryo-electron crystallography data indicate that helices 6 and 12 of P-glycoprotein are closer in P-glycoprotein than in the crystal structure of Sav1866. Using homology modelling we present evidence that the

• Báo cáo khoa học
• medical reports
• thesis report
• traditional medicine
• medical knowledge
• medical research
• analysis of cytoplasmic
• statements and documents scientific reports
• clinical trials
• medical management
• health care
• medical transfer
• the developing countries