Fe(II)/Fe(III) Redox Process Can Significantly Modulate the Conformational Dynamics and Electrostatics of Pirin in NF-κB Regulation.

ABSTRACT: Pirin is an iron (Fe)-dependent regulatory protein of nuclear factor κB (NF-κB) transcription factors. Binding studies have suggested that the oxidative state of iron plays a crucial role in modulating the binding of Pirin to NF-κB p65, in turn enhancing the binding of p65 to DNA. The Fe(III) form of Pirin is the active form and binds to NF-κB, whereas the Fe(II) form does not bind to NF-κB. However, the surprising consequence of a single charge perturbation in the functional modulation of NF-κB is not well understood. Here, we use quantum mechanical calculations and microsecond-long molecular dynamics simulations to explore the free-energy landscapes of the Fe(II) and Fe(III) forms of Pirin. We show that the restricted conformational space and electrostatic complementarity of the Fe(III)

SUBMITTER: Barman A 

PROVIDER: S-EPMC6640773 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature