Influence of β-Sheet Structure on the Susceptibility of Proteins to Backbone Oxidative Damage: Preference for αC-Centered Radical Formation at Glycine Residues of Antiparallel β-Sheets

Abstract

Ab initio calculations at the B3LYP/6-31G(d) level of theory were carried out on selected cyclic hydrogen-bonded (H-bonded) dimers of glycine and alanine as models for β-sheets and on the αC-centered radicals derived from them. The structures mirrored the cycles found in the H-bonded network of parallel and antiparallel β-sheet secondary structure, and were otimized both with and without enforcement of constraints on the Φ,Ψ torsion angles. Transition structures for the migration of an H atom from an αC site to another αC site or to an S atom were located. It was found that the presence of a H-bonded strand of a β-sheet has little effect on the αC−H bond dissociation enthalpy (BDE) of glycine but raises the BDE of other residues by a significant amount. The parallel β-sheet structure and Φ,Ψ angles lead to a significant increase in BDE, relative to the random coil structure, due to loss of captodative stabilization. The antiparallel β-sheet structure and Φ,Ψ angles do not lead to a significant increase in...