Divalent ions as mediators of carbonylation in cardiac myosin binding protein C

Published

November 1, 2023

Author(s)

Christina Bergonzo, Baikuntha Aryal, Ashutosh Rao

Abstract

The dosing and efficacy of chemotherapeutic drugs can be limited by toxicity caused by off-pathway reactions. One hypothesis for how such toxicity arises is via metal-catalyzed oxidative damage of cardiac myosin binding protein C (cMyBP-C) found in cardiac tissue. Previous research indicates that metal ion mediated reactive oxygen species induce high levels of protein carbonylation, changing the structure and function of this protein. In this work, we use long timescale all-atom molecular dynamics simulations to investigate the ion environment surrounding the C0 and C1 subunits of cMyBP-C responsible for actin binding. We show that divalent cations are colocalized with protein carbonylation-prone amino acid residues and that carbonylation of these residues can lead to site-specific interruption to the actin-cMyBP-C binding.

Citation

Journal of Molecular Graphics and Modelling

Volume

124

Pub Type

Journals

Download Paper

https://doi.org/10.1016/j.jmgm.2023.108576

Local Download

Keywords

protein carbonylation, metal ion-induced ROS, molecular dynamics, cMyBP-C

Citation

Bergonzo, C. , Aryal, B. and Rao, A. (2023), Divalent ions as mediators of carbonylation in cardiac myosin binding protein C, Journal of Molecular Graphics and Modelling, [online], https://doi.org/10.1016/j.jmgm.2023.108576, https://tsapps.nist.gov/publication/get_pdf.cfm?pub_id=936532 (Accessed November 10, 2024)