Molecular basis of a redox switch: molecular dynamics simulations and surface plasmon resonance provide insight into reduced and oxidised angiotensinogen.
Jennifer M Crowther, Letitia H Gilmour, Benjamin T Porebski, Sarah G Heath, Neil R Pattinson, Maurice C Owen, Rayleen Fredericks, Ashley M Buckle, Conan J Fee, Christoph Göbl, Renwick CJ Dobson
Biochem J | Published : 2021
Angiotensinogen fine-tunes the tightly controlled activity of the renin-angiotensin system by modulating the release of angiotensin peptides that control blood pressure. One mechanism by which this modulation is achieved is via angiotensinogen's Cys18-Cys138 disulfide bond that acts as a redox switch. Molecular dynamics simulations of each redox state of angiotensinogen reveal subtle dynamic differences between the reduced and oxidised forms, particularly at the N-terminus. Surface plasmon resonance data demonstrate that the two redox forms of angiotensinogen display different binding kinetics to an immobilised anti-angiotensinogen monoclonal antibody. Mass spectrometry mapped the epitope fo..View full abstract