SNOSite: exploiting maximal dependence decomposition to identify cysteine S-nitrosylation with substrate site specificity - PubMed (original) (raw)

SNOSite: exploiting maximal dependence decomposition to identify cysteine S-nitrosylation with substrate site specificity

Tzong-Yi Lee et al. PLoS One. 2011.

Abstract

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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1

Figure 1. The flowchart of MDD clustering.

Figure 2

Figure 2. Frequency plot of sequence logo of S-nitrosylation sites with 21-mer window length.

Figure 3

Figure 3. The compositional biases of amino acids around S-nitrosylation sites compared to the non-S-nitrosylation sites.

The amino acids that are significantly enriched or depleted (_P_-value<0.05) around S-nitrosylation sites are presented.

Figure 4

Figure 4. Comparison of average percentage of ASA in the 21-mer window (−10∼+10) between S-nitrosylation and non-S-nitrosylation sites.

Figure 5

Figure 5. The top twenty physicochemical properties of S-nitrosylation sites ranked by the average value of F-score measurement in 21-mer window.

KRIW710101, side chain interaction parameter ; OOBM850105, optimized side chain interaction parameter ; FINA910104, helix termination parameter at position j+1 ; FAUJ880111, positive charge ; GUYH850104, apparent partition energies calculated from Janin index ; KIDA850101, hydrophobicity-related index ; GUYH850101, partition energy ; JANJ780101, average accessible surface area ; ROSM880102, side chain hydropathy ; CHOC760102, residue accessible surface area in folded protein ; FASG890101, hydrophobicity index ; RACS820103, average relative fractional occurrence in AL(i) ; KARP850103, flexibility parameter for two rigid neighbors ; OOBM770101, average non-bonded energy per atom ; LEVM760101, hydrophobic parameter ; MEIH800102, average reduced distance for side chain ; GUYH850105, apparent partition energies calculated from Chothia index ; KRIW790102, fraction of site occupied by water ; PUNT030101, knowledge-based membrane-propensity scale from 1D_Helix in MPtopo databases ; WEBA780101, RF value in high salt chromatography .

Figure 6

Figure 6. A case study of Bos taurus dimethylarginine dimethylaminohydrolase 1 (DDAH1) which contains two S-nitrosylation sites at positions 222 and 274.

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References

    1. Bogdan C. Nitric oxide and the immune response. Nat Immun. 2001;2:907–916. - PubMed
    1. Karpuzoglu E, Ahmed SA. Estrogen regulation of nitric oxide and inducible nitric oxide synthase (iNOS) in immune cells: Implications for immunity, autoimmune diseases, and apoptosis. Nitric Oxide. 2006;15:177–186. - PubMed
    1. Lindermayr C, Saalbach G, Durner J. Proteomic identification of S-nitrosylated proteins in Arabidopsis. Plant Physiol. 2005;137:921–930. - PMC - PubMed
    1. Gaston B, Singel D, Doctor A, Stamler JS. S-nitrosothiol signaling in respiratory biology. Am J Respir Crit Care Med. 2006;173:1186–1193. - PMC - PubMed
    1. Stamler JS, Lamas S, Fang FC. Nitrosylation. the prototypic redox-based signaling mechanism. Cell. 2001;106:675–683. - PubMed

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