Origin of Nitric Oxide Reduction Activity in Flavo–Diiron NO Reductase: Key Roles of the Second Coordination Sphere. Issue 12 (14th February 2019)

• Record Type: Journal Article
• Authors: Lu, Jiarui; Bi, Bo; Lai, Wenzhen; Chen, Hui
• Is Part Of: Angewandte Chemie international edition. Volume 58:Issue 12(2019)
• Page Start: 3795
• Page End: 3799
• Publication Date: 2019-02-14
• Subjects: flavo–diiron protein -- N–N formation -- N–O cleavage -- NO reduction -- second coordination sphere; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201812343
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: The second coordination sphere constitutes a distinguishing factor in the active site to modulate enzymatic reactivity. To unravel the origin of NO‐to‐N2 O reduction activity of non‐heme diiron enzymes, herein we report a strong second‐coordination‐sphere interaction between a conserved Tyr197 and the key iron–nitrosyl intermediate of Tm FDP (flavo–diiron protein), which leads to decreased reaction barriers towards N–N formation and N–O cleavage in NO reduction. This finding supports the direct coupling of diiron dinitrosyl as the N–N formation mode in our QM/MM modeling, and reconciles the mechanistic controversy of external reduction between FDPs and synthetic biomimetics of the iron–nitrosyls. This work highlights the application of QM/MM 57 Fe Mössbauer modeling in elucidating the structural features of not only first, but also second coordination spheres of the key transient species involved in NO/O2 activation by non‐heme diiron enzymes. Abstract : A second chance : QM/MM spectroscopic and mechanistic modeling reveal that the second coordination sphere effect, originating from a conserved tyrosine residue, can significantly enhance the activity of flavo–diiron NO reductase. This finding helps to decipher the mechanistic origin of the NO reductase activity in flavo–diiron proteins, which also reconciles the external reductant controversy in NO reduction chemistry of iron–nitrosyls.