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

Bignon, Emmanuelle, Rizza, Salvatore, Filomeni, Giuseppe, Papaleo, Elena
Computational and Structural Biotechnology Journal 2019 v.17 pp. 415-429
NADP (coenzyme), arginine, biotechnology, citrulline, endothelial nitric oxide synthase, inducible nitric oxide synthase, neuronal nitric oxide synthase, nitric oxide, oxidation, oxygen
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.