Effect of 4-HNE Modification on ZU5-ANK Domain and the Formation of Their Complex with β-Spectrin: A Molecular Dynamics Simulation Study
Autor: | Humberto Pérez-González, Ricardo Vivas-Reyes, Darío Méndez-Cuadro, Erika Rodríguez-Cavallo, Rodrigo Galindo-Murillo, Antistio Alviz-Amador |
---|---|
Rok vydání: | 2019 |
Předmět: |
Ankyrins
Erythrocytes General Chemical Engineering Lysine Binding energy Molecular Dynamics Simulation Library and Information Sciences medicine.disease_cause 01 natural sciences Molecular dynamics symbols.namesake Protein Domains 0103 physical sciences medicine Humans Ankyrin Spectrin chemistry.chemical_classification Aldehydes 010304 chemical physics General Chemistry 0104 chemical sciences Computer Science Applications Oxidative Stress 010404 medicinal & biomolecular chemistry chemistry Biophysics symbols van der Waals force Carbonylation Oxidative stress Protein Binding |
Zdroj: | Journal of Chemical Information and Modeling. 60:805-820 |
ISSN: | 1549-960X 1549-9596 |
Popis: | 4-HNE-modified ankyrins have been described in diseases such as diabetes, renal failure, G6PD deficient, sickle cell trait, and P. falciparum infected erythrocytes with different AB0 blood groups. However, effects at the atomic level of this carbonylation on structure and function of modified protein are not yet fully understood. We present a study based on molecular dynamics simulations of nine 4-HNE modified residues of the ZU5-ANK ankyrin domain with β-spectrin and their binding energy profiles. Results show that 4-HNE induced local conformational changes over all protein systems evaluated, increased mobility in the modification sites, and localized structural changes between the positively charged patch of the ZU5-ANK domain. Carbonylation with 4-HNE on lysine residues decreased the affinity between ZU5-ANK and the 14-β-spectrin repeat by reducing electrostatic and van der Waals interactions. The presented work provides further insight into understanding the loss of human erythrocyte deformation capacity under conditions of oxidative stress in different diseases. |
Databáze: | OpenAIRE |
Externí odkaz: |