Physical basis for the ofloxacin-induced acceleration of lysozyme aggregation and polymorphism in amyloid fibrils
| Autor: | Shivani A. Muthu, Sonali M. Shiriskar, Nivin Mothi, Basir Ahmad, Raghuvir R. S. Pissurlenkar, Anil Kumar |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Amyloid Ofloxacin Protein Conformation Globular protein Biophysics Plasma protein binding Protein aggregation Fibril Biochemistry Protein Aggregates 03 medical and health sciences chemistry.chemical_compound Protein structure medicine Binding site Molecular Biology chemistry.chemical_classification Binding Sites 030102 biochemistry & molecular biology Chemistry Enzyme Activation Molecular Docking Simulation 030104 developmental biology Muramidase Lysozyme Crystallization Hydrophobic and Hydrophilic Interactions Protein Binding medicine.drug |
| Zdroj: | Archives of Biochemistry and Biophysics. 592:10-19 |
| ISSN: | 0003-9861 |
| DOI: | 10.1016/j.abb.2016.01.005 |
| Popis: | Aggregation of globular proteins is an intractable problem which generally originates from partially folded structures. The partially folded structures first collapse non-specifically and then reorganize into amyloid-like fibrils via one or more oligomeric intermediates. The fibrils and their on/off pathway intermediates may be toxic to cells and form toxic deposits in different human organs. To understand the basis of origins of the aggregation diseases, it is vital to study in details the conformational properties of the amyloidogenic partially folded structures of the protein. In this work, we examined the effects of ofloxacin, a synthetic fluoroquinolone compound on the fibrillar aggregation of hen egg-white lysozyme. Using two aggregation conditions (4M GuHCl at pH 7.0 and 37 °C; and pH 1.7 at 65 °C) and a number of biophysical techniques, we illustrate that ofloxacin accelerates fibril formation of lysozyme by binding to partially folded structures and modulating their secondary, tertiary structures and surface hydrophobicity. We also demonstrate that Ofloxacin-induced fibrils show polymorphism of morphology, tinctorial properties and hydrophobic surface exposure. This study will assist in understanding the determinant of fibril formation and it also indicates that caution should be exercised in the use of ofloxacin in patients susceptible to various aggregation diseases. |
| Databáze: | OpenAIRE |
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