Ca(2+) binding to c-state of adenine nucleotide translocase (ANT)-surrounding cardiolipins enhances (ANT)-Cys(56) relative mobility: a computational-based mitochondrial permeability transition study
| Autor: | Antonio Carlos dos Santos, Carlos Curti, Fernando P. Rodrigues, Carlos Henrique Tomich de Paula da Silva, Cezar R. Pestana, Sérgio Akira Uyemura, Gilberto L. Pardo-Andreu |
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| Rok vydání: | 2008 |
| Předmět: |
ADP
Male Models Molecular Computational chemistry Cell Membrane Permeability Protein Conformation Succinic Acid Mitochondria Liver Biochemistry Mitochondrial Membrane Transport Proteins chemistry.chemical_compound Cardiolipin Translocase Mitochondrial permeability transition biology Adenine nucleotide translocase food and beverages ANT Adenosine Diphosphate Cardiolipins behavior and behavior mechanisms Cyclosporine ATP–ADP translocase Immunosuppressive Agents Stereochemistry Biophysics Molecular dynamics Animals Computer Simulation Cysteine Mitochondrion Rats Wistar Molecular interaction field Mitochondrial Permeability Transition Pore fungi Cell Biology biochemical phenomena metabolism and nutrition Permeability transition pore Rats Oxidative Stress Mitochondrial permeability transition pore chemistry Models Chemical Permeability (electromagnetism) Helix biology.protein Calcium Mitochondrial Swelling Mitochondrial ADP ATP Translocases |
| Zdroj: | Biochimica et biophysica acta. 1787(3) |
| ISSN: | 0006-3002 |
| Popis: | The oxidation of critical cysteines/related thiols of adenine nucleotide translocase (ANT) is believed to be an important event of the Ca 2+ -induced mitochondrial permeability transition (MPT), a process mediated by a cyclosporine A/ADP-sensitive permeability transition pores (PTP) opening. We addressed the ANT-Cys 56 relative mobility status resulting from the interaction of ANT/surrounding cardiolipins with Ca 2+ and/or ADP by means of computational chemistry analysis (Molecular Interaction Fields and Molecular Dynamics studies), supported by classic mitochondrial swelling assays. The following events were predicted: (i) Ca 2+ interacts preferentially with the ANT surrounding cardiolipins bound to the H4 helix of translocase, (ii) weakens the cardiolipins/ANT interactions and (iii) destabilizes the initial ANT-Cys 56 residue increasing its relative mobility. The binding of ADP that stabilizes the conformation “m” of ANT and/or cardiolipin, respectively to H5 and H4 helices, could stabilize their contacts with the short helix h56 that includes Cys 56 , accounting for reducing its relative mobility. The results suggest that Ca 2+ binding to adenine nucleotide translocase (ANT)-surrounding cardiolipins in c-state of the translocase enhances (ANT)-Cys 56 relative mobility and that this may constitute a potential critical step of Ca 2+ -induced PTP opening. |
| Databáze: | OpenAIRE |
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