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

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.

Potential anti-inflammatory activity of walnut protein derived peptide leucine-proline-phenylalanine in lipopolysaccharides-irritated RAW264.7 cells

“…The residue Arg-375 is a key amino acid to regulate H 4 B which contributes to electron transfer and stability of dimer (Cinelli et al, 2020). Cofactor heme (HEM 901) is the catalytic centre that oxidizes L-arginine to L-citrulline, it also serves as an anchor and plays a key role in the electron transfer chain (Bignon et al, 2019). Additionally, it has been reported that Arg-260 and Gln-257 were the targeted residues of novel NO inhibitors (Wang et al, 2017).…”

Understanding the Role of Endothelial Glycocalyx in Mechanotransduction via Computational Simulation: A Mini Review

“…In principle, the hierarchy of numerical methods can all be developed to reproduce the biochemical processes in mechanotransduction. For example, quantum mechanics/molecular mechanics (QM/MM) computations, which fall under microscopic methods (subatomic scale, to be precise) and advances in probing the electron transfer process, can be applied to find reaction mechanisms of enzymes, like the activation of eNOS (endothelial nitric oxide synthase) as reviewed in Bignon et al (2019). Also, reactive force field MD (Senftle et al, 2016) simulations, which uses QM-trained force fields to mimic bond breaking and formation and have been extensively proved to be effective in capturing reaction pathways, can be applied to work out the chain reactions after the release of Ca 2+ initiated by mechanotransduction.…”

Liubao Insect tea polyphenols prevent HCl/ethanol induced gastric damage through its antioxidant ability in mice

“…nNOS, eNOS and iNOS are the neurotype, endothelial type and inducible type of NOS, respectively. 38 Under normal physiological conditions, the mechanism of NO production, release, diffusion and inactivation is precisely regulated in the nervous system, which is mainly achieved by regulating the activation and deactivation of nNOS. 39 nNOS not only plays an important role in the nervous system, but is also distributed in gastric mucosal epithelial cells.…”