title: Protein control of S-nitrosothiol reactivity: interplay of antagonistic resonance structures.
abstract: There is currently great interest in S-nitrosothiols (RSNOs) because  formation of protein-based RSNOs-protein S-nitrosation-has been recently recognized as a major pathway of the biological function of nitric oxide, NO. Despite the growing number of S-nitrosated proteins identified in vivo, enzymatic processes that control reactions of biological RSNOs are still not well understood. In this article, we use a range of models to computationally demonstrate that specific interactions of RSNOs with charged and polar residues in proteins can result in dramatic modification of RSNO structure, stability, and reactivity. This unprecedented sensitivity of the -SNO group toward interactions with charged species is related to their unusual electronic structure that can be elegantly expressed in terms of antagonistic resonance structures. We propose a 'ligand effect map' (LEM) approach as an efficient way to estimate the environment effects on the -SNO groups in proteins without performing electronic structure calculations. Furthermore, the calculated (15)N NMR signatures of these specific interactions suggest that (15)N NMR spectroscopy can be an effective technique to identify and study these interactions experimentally. Overall, the results of this study suggest that RSNO reactions in vivo should be tightly controlled by the protein environment via modulation of the RSNO electronic structure.
authors: Department of Chemistry, Marquette University, P.O. Box 1881, Milwaukee, Wisconsin 53201-1881, USA.
authors: Marat R
authors: MR
authors: Talipov
authors: Qadir K
authors: QK
authors: Timerghazin
mesh_terms: D004583:Electrons; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D009569:Nitric Oxide / Q000737:chemistry / Q000378:metabolism; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D026403:S-Nitrosothiols / Q000737:chemistry*; D013879:Thioredoxins / Q000737:chemistry / Q000378:metabolism
chemical_list: D011506:Proteins; D026403:S-Nitrosothiols; D009569:Nitric Oxide; D013879:Thioredoxins