SNOSite: Exploiting Maximal Dependence Decomposition to Identify Cysteine S-Nitrosylation with Substrate Site Specificity

S-nitrosylation, the covalent attachment of a nitric oxide to (NO) the sulfur atom of cysteine, is a selective and reversible protein post-translational modification (PTM) that regulates protein activity, localization, and stability. Despite its implication in the regulation of protein functions and cell signaling, the substrate specificity of cysteine S-nitrosylation remains unknown. Based on a total of 586 experimentally identified S-nitrosylation sites from SNAP/L-cysteine-stimulated mouse endothelial cells, this work presents an informatics investigation on S-nitrosylation sites including structural factors such as the flanking amino acids composition, the accessible surface area (ASA) and physicochemical properties, i.e. positive charge and side chain interaction parameter. Due to the difficulty to obtain the conserved motifs by conventional motif analysis, maximal dependence decomposition (MDD) has been applied to obtain statistically significant conserved motifs. Support vector machine (SVM) is applied to generate predictive model for each MDD-clustered motif. According to five-fold cross-validation, the MDD-clustered SVMs could achieve an accuracy of 0.902, and provides a promising performance in an independent test set. The effectiveness of the model was demonstrated on the correct identification of previously reported S-nitrosylation sites of Bos taurus dimethylarginine dimethylaminohydrolase 1 (DDAH1) and human hemoglobin subunit beta (HBB). Finally, the MDD-clustered model was adopted to construct an effective web-based tool, named SNOSite (http://csb.cse.yzu.edu.tw/SNOSite/), for identifying S-nitrosylation sites on the uncharacterized protein sequences

The Davydov/Scott Model for Energy Storage and Transport in Proteins

The current status of the Davydov/Scott model for energy transfer in proteins is reviewed. After a brief introduction to the theoretical framework and to the basic results, the problems of finite temperature dynamics and of the full quantum and mixed quantum-classical approximations are described, as well as recent results obtained within each of these approximations. A short survey of experimental evidence in support of the Davydov/Scott model is made and absorption spectra are calculated that show the same temperature dependence as that measured in crystalline acetanilide. Future applications of the Davydov/Scott model to protein folding and function and to misfolding diseases are outlined

The solution structure of the histidine-containing protein (HPr) from Staphylococcus aureus as determined by two-dimensional ¹H-NMR spectroscopy

The three-dimensional solution structure of the heat-stable phosphocarrier protein HPr from Staphylococcus aureus was determined from two-dimensional NMR data by restrained molecular dynamics. It consists of a large twisted antiparallel beta-pleated sheet with four strands A, B, C, and D of amino acids 2-7, 34-37, 40-42 and 60-65. Three right-handed helices A, B, C (amino acids 18-27, 47-53 and 71-85) are positioned on top of this sheet. The aromatic ring of His15 is located in a cleft formed by amino acids 12-17 and 55-58, only the nitrogen (N delta 1) atom which can be phosphorylated by enzyme I is exposed to the water. The side chains of Thr12 and Arg17 are located close to the histidine ring. The regulatory serine residue (Ser46) is located in a hydrophobic patch, its hydroxyl group is water-accessible but forms hydrogen bonds with the amide groups of the backbone. The general features of the three-dimensional structure are similar to those found in HPr proteins from different microorganisms such as Escherichia coli, Bacillus subtilis and Streptococcus faecalis