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A protein microarray-based analysis of S-nitrosylation.

Publication ,  Journal Article
Foster, MW; Forrester, MT; Stamler, JS
Published in: Proc Natl Acad Sci U S A
November 10, 2009

The ubiquitous cellular influence of nitric oxide (NO) is exerted substantially through protein S-nitrosylation. Whereas NO is highly promiscuous, physiological S-nitrosylation is typically restricted to one or very few Cys residue(s) in target proteins. The molecular basis for this specificity may derive from properties of the target protein, the S-nitrosylating species, or both. Here, we describe a protein microarray-based approach to investigate determinants of S-nitrosylation by biologically relevant low-mass S-nitrosothiols (SNOs). We identify large sets of yeast and human target proteins, among which those with active-site Cys thiols residing at N termini of alpha-helices or within catalytic loops were particularly prominent. However, S-nitrosylation varied substantially even within these families of proteins (e.g., papain-related Cys-dependent hydrolases and rhodanese/Cdc25 phosphatases), suggesting that neither secondary structure nor intrinsic nucleophilicity of Cys thiols was sufficient to explain specificity. Further analyses revealed a substantial influence of NO-donor stereochemistry and structure on efficiency of S-nitrosylation as well as an unanticipated and important role for allosteric effectors. Thus, high-throughput screening and unbiased proteome coverage reveal multifactorial determinants of S-nitrosylation (which may be overlooked in alternative proteomic analyses), and support the idea that target specificity can be achieved through rational design of S-nitrosothiols.

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Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

November 10, 2009

Volume

106

Issue

45

Start / End Page

18948 / 18953

Location

United States

Related Subject Headings

  • Yeasts
  • Ubiquitin Thiolesterase
  • Thiosulfate Sulfurtransferase
  • Substrate Specificity
  • S-Nitrosothiols
  • Proteomics
  • Proteins
  • Protein Tyrosine Phosphatases
  • Protein Array Analysis
  • Nitric Oxide
 

Citation

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Foster, M. W., Forrester, M. T., & Stamler, J. S. (2009). A protein microarray-based analysis of S-nitrosylation. Proc Natl Acad Sci U S A, 106(45), 18948–18953. https://doi.org/10.1073/pnas.0900729106
Foster, Matthew W., Michael T. Forrester, and Jonathan S. Stamler. “A protein microarray-based analysis of S-nitrosylation.Proc Natl Acad Sci U S A 106, no. 45 (November 10, 2009): 18948–53. https://doi.org/10.1073/pnas.0900729106.
Foster MW, Forrester MT, Stamler JS. A protein microarray-based analysis of S-nitrosylation. Proc Natl Acad Sci U S A. 2009 Nov 10;106(45):18948–53.
Foster, Matthew W., et al. “A protein microarray-based analysis of S-nitrosylation.Proc Natl Acad Sci U S A, vol. 106, no. 45, Nov. 2009, pp. 18948–53. Pubmed, doi:10.1073/pnas.0900729106.
Foster MW, Forrester MT, Stamler JS. A protein microarray-based analysis of S-nitrosylation. Proc Natl Acad Sci U S A. 2009 Nov 10;106(45):18948–18953.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

November 10, 2009

Volume

106

Issue

45

Start / End Page

18948 / 18953

Location

United States

Related Subject Headings

  • Yeasts
  • Ubiquitin Thiolesterase
  • Thiosulfate Sulfurtransferase
  • Substrate Specificity
  • S-Nitrosothiols
  • Proteomics
  • Proteins
  • Protein Tyrosine Phosphatases
  • Protein Array Analysis
  • Nitric Oxide