Insights into the Dynamics and Dissociation Mechanism of a Protein Redox Complex Using Molecular Dynamics.

Leishmania major peroxidase (LmP) is structurally and functionally similar to the well-studied yeast Cytochrome c peroxidase (CCP). A recent Brownian dynamics study showed that L. major Cytochrome c (LmCytc) associates with LmP by forming an initial complex with the N-terminal helix A of LmP, followed by a movement toward the electron transfer (ET) site observed in the LmP-LmCytc crystal structure.

"Bind and Crawl" Association Mechanism of Leishmania major Peroxidase and Cytochrome c Revealed by Brownian and Molecular Dynamics Simulations.

Leishmania major, the parasitic causative agent of leishmaniasis, produces a heme peroxidase (LmP), which catalyzes the peroxidation of mitochondrial cytochrome c (LmCytc) for protection from reactive oxygen species produced by the host. The association of LmP and LmCytc, which is known from kinetics measurements to be very fast (∼10(8) M(-1) s(-1)), does not involve major conformational changes and has been suggested to be dominated by electrostatic interactions. We used Brownian dynamics simulations to investigate the mechanism of formation of the LmP-LmCytc complex.

Enzymatic Mechanism of Leishmania major Peroxidase and the Critical Role of Specific Ionic Interactions.

Leishmania major peroxidase (LmP) is very similar to the well-known yeast cytochrome c peroxidase (CcP). Both enzymes catalyze the peroxidation of cytochrome c. Like CcP, LmP reacts with H2O2 to form Compound I, which consists of a ferryl heme and a Trp radical, Fe(IV)═O;Trp(•+).