Use of Computational Biochemistry for Elucidating Molecular Mechanisms of Nitric Oxide Synthase

Emmanuelle Bignon; Salvatore Rizza; Giuseppe Filomeni; Elena Papaleo

doi:10.1016/j.csbj.2019.03.011

Use of Computational Biochemistry for Elucidating Molecular Mechanisms of Nitric Oxide Synthase

Comput Struct Biotechnol J. 2019 Mar 23:17:415-429. doi: 10.1016/j.csbj.2019.03.011. eCollection 2019.

Authors

Emmanuelle Bignon¹, Salvatore Rizza², Giuseppe Filomeni^{2

3}, Elena Papaleo^{1

4}

Affiliations

¹ Computational Biology Laboratory, Danish Cancer Society Research Center, Strandboulevarden 49, 2100 Copenhagen, Denmark.
² Redox Signaling and Oxidative Stress Group, Cell Stress and Survival Unit, Danish Cancer Society Research Center, Strandboulevarden 49, 2100 Copenhagen, Denmark.
³ Department of Biology, University of Rome Tor Vergata, Rome, Italy.
⁴ Translational Disease Systems Biology, Faculty of Health and Medical Sciences, Novo Nordisk Foundation Center for Protein Research University of Copenhagen, Copenhagen, Denmark.

Abstract

Nitric oxide (NO) is an essential signaling molecule in the regulation of multiple cellular processes. It is endogenously synthesized by NO synthase (NOS) as the product of L-arginine oxidation to L-citrulline, requiring NADPH, molecular oxygen, and a pterin cofactor. Two NOS isoforms are constitutively present in cells, nNOS and eNOS, and a third is inducible (iNOS). Despite their biological relevance, the details of their complex structural features and reactivity mechanisms are still unclear. In this review, we summarized the contribution of computational biochemistry to research on NOS molecular mechanisms. We described in detail its use in studying aspects of structure, dynamics and reactivity. We also focus on the numerous outstanding questions in the field that could benefit from more extensive computational investigations.

Keywords: Nitric oxide synthase; computational methods; molecular mechanisms; redox regulation.

Publication types

Review