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A motif for reversible nitric oxide interactions in metalloenzymes

Nature Chemistry volume 8, pages 663–669 (2016)Cite this article

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Abstract

Nitric oxide (NO) participates in numerous biological processes, such as signalling in the respiratory system and vasodilation in the cardiovascular system. Many metal-mediated processes involve direct reaction of NO to form a metal–nitrosyl (M–NO), as occurs at the Fe2+ centres of soluble guanylate cyclase or cytochrome c oxidase. However, some copper electron-transfer proteins that bear a type 1 Cu site (His2Cu–Cys) reversibly bind NO by an unknown motif. Here, we use model complexes of type 1 Cu sites based on tris(pyrazolyl)borate copper thiolates [CuII]-SR to unravel the factors involved in NO reactivity. Addition of NO provides the fully characterized S-nitrosothiol adduct [CuI](κ1-N(O)SR), which reversibly loses NO on purging with an inert gas. Computational analysis outlines a low-barrier pathway for the capture and release of NO. These findings suggest a new motif for reversible binding of NO at bioinorganic metal centres that can interconvert NO and RSNO molecular signals at copper sites.

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Figure 1: T1Cu electron-transfer site and synthetic model complexes.
Figure 2: Capture of NO by iPr2TpCu-SCPh3 (1a) to form unstable S-nitrosothiol adduct 1b.
Figure 3: Synthesis of MesTpCu(κ1-N(O)SCPh3) (2b) and MesTpCu-SCPh3 (1b).
Figure 4: X-ray crystal structures of MesTpCu-SCPh3 (1b) and MesTpCu(κ1-N(O)SCPh3) (2b).
Figure 5: Orbital interactions and pathway for reversible capture of NO by MesTpCu-SCPh3 (2b).
Figure 6: Interconnections between NO and S-nitrosothiols promoted by copper.

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Acknowledgements

This material is based on work supported by the US National Science Foundation (award no. CHE-1459090, to T.H.W.). The authors thank the Purdue University Department of Chemistry and the Vorisek Endowment at Georgetown University for additional financial support (to T.H.W.), as well as the TUBITAK ULAKBIM High Performance and Grid Computing Center (TRUBA, Turkey) for computer time (N.Ç.-O.).

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Authors and Affiliations

  1. Department of Chemistry, Georgetown University, Box 571227, Washington, 20057, DC, USA

    Shiyu Zhang, Marie M. Melzer & Timothy H. Warren

  2. Department of Chemical Engineering, Yeditepe University, Istanbul, 34755, Turkey

    S. Nermin Sen & Nihan Çelebi-Ölçüm

  3. Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, 47907, Indiana, USA

    Timothy H. Warren

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Contributions

S.Z., N.Ç.-Ö. and T.H.W. conceived and designed the research. S.Z., M.M.M., S.N.S. and N.Ç.-Ö. collected data and performed calculations. S.Z., M.M.M., S.N.S., N.Ç.-Ö. and T.H.W. analysed the data. S.Z., N.Ç.-Ö. and T.H.W. co-wrote the paper.

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Correspondence to Nihan Çelebi-Ölçüm or Timothy H. Warren.

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Supplementary information

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Supplementary information (PDF 5913 kb)

Supplementary information

Crystallographic data for compound MesTpCu-SCPh3 (1b) (CIF 1080 kb)

Supplementary information

Crystallographic data for compound MesTpCu(κ1-N(O)SCPh3) (2b) (CIF 1541 kb)

Supplementary information

Crystallographic data for compound iPr2TpCuI(CNAr2,6-Me2) (3a) (CIF 1461 kb)

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Zhang, S., Melzer, M., Sen, S. et al. A motif for reversible nitric oxide interactions in metalloenzymes. Nature Chem 8, 663–669 (2016). https://doi.org/10.1038/nchem.2502

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