Oxidative HNO Formation Mechanisms from NH₂OH via Two Different Heme Proteins and Effects from Hemes, Nearby Residues, and Protein Environments.

ABSTRACT: Nitroxyl (HNO) is a biologically active nitrogen oxide with therapeutic potential for several disorders, but its endogenous formation remains poorly understood. Previous experimental work showed that hydroxylamine (NH₂OH), a possible physiological precursor, was oxidized by hydrogen peroxide (H₂O₂) activated heme proteins to produce HNO. In this study, we employed both density functional theory (DFT) and hybrid quantum mechanics and molecular mechanics (QM/MM) calculations to investigate the reaction mechanisms of HNO generation from NH₂OH via two representative heme proteins, myoglobin (Mb) and catalase (CAT), with neutral and negative axial ligands. Various structural models to successively include more components of the proteins were studied t

SUBMITTER: Shi Y 

PROVIDER: S-EPMC12593048 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature