%0 Journal Article
%T Comparison of the Nitric Oxide Synthase Interactomes and S-Nitroso-Proteomes: Furthering the Case for Enzymatic S-Nitrosylation.
%A Seth D
%A Stomberski CT
%A McLaughlin PJ
%A Premont RT
%A Lundberg K
%A Stamler JS
%J Antioxid Redox Signal
%V 39
%N 10
%D 10 2023 1
%M 37053107
%F 7.468
%R 10.1089/ars.2022.0199
%X Aims: S-nitrosylation of proteins is the main mechanism through which nitric oxide (NO) regulates cellular function and likely represents the archetype redox-based signaling system across aerobic and anaerobic organisms. How NO generated by different nitric oxide synthase (NOS) isoforms leads to specificity of S-nitrosylation remains incompletely understood. This study aimed to identify proteins interacting with, and whose S-nitrosylation is mediated by, human NOS isoforms in the same cellular system, thereby illuminating the contribution of individual NOSs to specificity. Results: Of the hundreds of proteins interacting with each NOS, many were also S-nitrosylated. However, a large proportion of S-nitrosylated proteins (SNO-proteins) did not associate with NOS. Moreover, most NOS interactors and SNO-proteins were unique to each isoform. The amount of NO produced by each NOS isoform was unrelated to the numbers of SNO-proteins. Thus, NOSs promoted S-nitrosylation of largely distinct sets of target proteins. Different signaling pathways were enriched downstream of each NOS. Innovation and Conclusion: The interactomes and SNOomes of individual NOS isoforms were largely distinct. Only a small fraction of SNO-proteins interacted with their respective NOS. Amounts of S-nitrosylation were unrelated to the amount of NO generated by NOSs. These data argue against free diffusion of NO or NOS interactions as being necessary or sufficient for S-nitrosylation and favor roles for additional enzymes and/or regulatory elements in imparting SNO-protein specificity. Antioxid. Redox Signal. 39, 621-634.