dbSNO 2.0: a resource for exploring structural environment, functional and disease association and regulatory network of protein S-nitrosylation

Abstract

Given the increasing number of proteins reported to be regulated by S-nitrosylation (SNO), it is considered to act, in a manner analogous to phosphorylation, as a pleiotropic regulator that elicits dual effects to regulate diverse pathophysiological processes by altering protein function, stability, and conformation change in various cancers and human disorders. Due to its importance in regulating protein functions and cell signaling, dbSNO (http://dbSNO.mbc.nctu.edu.tw) is extended as a resource for exploring structural environment of SNO substrate sites and regulatory networks of S-nitrosylated proteins. An increasing interest in the structural environment of PTM substrate sites motivated us to map all manually curated SNO peptides (4165 SNO sites within 2277 proteins) to PDB protein entries by sequence identity, which provides the information of spatial amino acid composition, solvent-accessible surface area, spatially neighboring amino acids, and side chain orientation for 298 substrate cysteine residues. Additionally, the annotations of protein molecular functions, biological processes, functional domains and human diseases are integrated to explore the functional and disease associations for S-nitrosoproteome. In this update, users are allowed to search a group of interested proteins/genes and the system reconstructs the SNO regulatory network based on the information of metabolic pathways and protein-protein interactions. Most importantly, an endogenous yet pathophysiological S-nitrosoproteomic dataset from colorectal cancer patients was adopted to demonstrate that dbSNO could discover potential SNO proteins involving in the regulation of NO signaling for cancer pathways.

Nitric Oxide: The Forgotten Child of Tumor Metabolism

“…Proteins are S-nitrosated when the thiol moiety of cysteine residues on peptides or proteins reversibly bind with NO to generate an S-nitrosothiols. This form of post-translational modification (PTM) is highly conserved and occurs in proteins in all biological systems [40]. S-nitrosation can control a diverse set of biological functions by regulating protein activity, altering protein localization, and mediating protein-protein interactions [41–43].…”

Nitrosative Stress, Hypernitrosylation, and Autoimmune Responses to Nitrosylated Proteins: New Pathways in Neuroprogressive Disorders Including Depression and Chronic Fatigue Syndrome

“…Redox-derived damage-associated molecular patterns (DAMPs), e.g. malondialdehyde, may trigger activation of the TLR complex, particularly TLR-2 and TLR-4 [162][163][164]. MDA for example attacks proteins leading to the formation of reactive carbonyl adducts [165], which behave as potent DAMPS [166].…”

Nitrosothiol-Trapping-Based Proteomic Analysis of S-Nitrosylation in Human Lung Carcinoma Cells

“…First, we compared our CysNO and cytokine data sets to dbSNO 2.0 (http://140.138.144.145/~dbSNO/index.php) a comprehensive resource of S-nitrosylated proteins from various organisms [40]. dbSNO lists a total of 720 human nitrosylated proteins.…”