HNO to NO Conversion Mechanism with Copper Zinc Superoxide Dismutase, Comparison with Heme Protein Mediated Conversions, and the Origin of Questionable Reversibility

Yelu Shi, Matthew A. Michael, Yong Zhang

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

The interconversion of NO and HNO, via copper zinc superoxide dismutase (CuZnSOD), is important in biomedicine and for HNO detection. Many mechanistic questions, including the decades-long debate on reversibility, were resolved in this work. Calculations of various active-site and full-protein models show that the basic mechanism is proton-coupled electron transfer with a computed barrier of 10.98 kcal mol−1, which is in excellent agreement with experimental results (10.62 kcal mol−1), and this nonheme protein-mediated reaction has many significant mechanistic differences compared with the conversions mediated by heme proteins due to geometric and electronic factors. The reasons for the irreversible nature of this conversion and models with the first thermodynamically favorable and kinetically feasible mechanism for the experimental reverse reaction were discovered. Such results are the first for nonheme enzyme mediated HNO to NO conversions, which shall facilitate other related studies and HNO probe development.

Original languageEnglish
Pages (from-to)5019-5027
Number of pages9
JournalChemistry - A European Journal
Volume27
Issue number15
DOIs
StatePublished - 12 Mar 2021

Keywords

  • computational chemistry
  • copper
  • enzymes
  • nitrogen oxides
  • reaction mechanisms

Fingerprint

Dive into the research topics of 'HNO to NO Conversion Mechanism with Copper Zinc Superoxide Dismutase, Comparison with Heme Protein Mediated Conversions, and the Origin of Questionable Reversibility'. Together they form a unique fingerprint.

Cite this