jz9b00403_si_001.pdf (228.24 kB)
Evidence of a Thermodynamic Ramp for Hole Hopping to Protect a Redox Enzyme from Oxidative Damage
journal contribution
posted on 2019-03-11, 00:00 authored by Laura Zanetti-Polzi, Isabella Daidone, Stefano CorniRedox
proteins and enzymes are at risk of irreversible oxidative
damage from highly oxidizing intermediates generated in the active
site in the case of unsuccessful functional reaction. Chains of tyrosine
and/or tryptophan residues have been recently proposed to provide
protection to the active site and the whole protein by delivering
oxidizing equivalents (holes) out of the protein via a multistep hopping
mechanism. In the present work we use a hybrid quantum/classical theoretical–computational
methodology based on the perturbed matrix method and on molecular
dynamics simulations to calculate the oxidation potential difference
along a chain of tyrosine and tryptophan residues in a human redox
enzyme of major importance, a superoxide dismutase, which acts as
antioxidant defense. We show that the hole hopping is thermodynamically
favored along such a chain and that the hopping propensity is strongly
affected by the protein environment and in particular by the active
site and its second coordination sphere.