dbSNO 2.0: a resource for exploring structural environment, functional and disease association and regulatory network of protein S-nitrosylation.
Bottom Line: 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.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.
Affiliation: Institute of Chemistry, Academia Sinica, Taipei 115, Taiwan.Show MeSH
Related in: MedlinePlus
Mentions: To enhance the utility of dbSNO resource, the web interface has been improved for users to browse and search efficiently for their proteins of interest. Supplementary Figure S4 shows the data content of a typical dbSNO entry. One of the aims in this update is to provide a platform for structural investigation of SNO substrate sites based on protein tertiary structures of PDB. Figure 2A presents a case study for investigating the spatial context around an SNO substrate site of Cys85 in the tertiary structure (PDB ID: 2LLT) of Protein S100-A1 (UniProtKB ID: S10A1_HUMAN). The tables of sequentially and structurally neighboring amino acids with side chain orientations are provided in Figure 2A and C, respectively. The table of top three nearest amino acids structurally neighboring the SNO substrate site of Cys85 is provided in Figure 2D. The surface area of Cys85 is also given in Figure 2E for the analysis of solvent accessibility. In order to provide a full investigation of structural acid-based motif (55) surrounding the SNO substrate site, the acid residues (K, R and H) and basic residues (D and E) are marked in blue and red, respectively, as shown in Figure 2F. The sequentially upstream (from positions −6 to −1) and downstream (from +1 to +6) amino acids, in which Asn86 (at position +1) contains the side chain orientation of 67.09° (as shown in Figure 2G) to the thiol group (SG) of Cys85 on the protein structure, are provided in Figure 2H. Figure 2I shows that the structurally neighboring amino acids, whose radial distance to the thiol group of Cys85 is less than 10 Å, are marked with highlighted blue on protein 3D structure. Furthermore, in the investigation of structurally neighboring amino acids, the top three nearest amino acids (Thr82, Asn86 and Phe44) with the information of accessible surface area and side chain orientation are provided in Figure 2J. Interestingly, Phe44 residue, which is distant to Cys85 in linear sequence, is accessible to protein surface area and contains the side chain orientation of 58.59°. This investigation indicates that Phe44 residue may provide significant influence on the binding of NO to Cys85. Additionally, five cases for local and global structure alignment between protein containing S-nitrosylated cysteine (SNC) and protein containing cysteine without NO binding are presented in Supplementary Figure S5.
Affiliation: Institute of Chemistry, Academia Sinica, Taipei 115, Taiwan.