Formation and Functions of Protein Sulfenic Acids

Leslie B. Poole1

1 Wake Forest University School of Medicine, Winston‐Salem, North Carolina
Publication Name:  Current Protocols in Toxicology
Unit Number:  Unit 17.1
DOI:  10.1002/0471140856.tx1701s18
Online Posting Date:  February, 2004
GO TO THE FULL TEXT: PDF or HTML at Wiley Online Library

Abstract

Protein sulfenic acids are generated as reversibly oxidized cysteinyl residues formed upon reaction of thiols with peroxides, nitric oxide, peroxynitrite, and other reactive oxygen or nitrogen species. They can be stabilized within the protein environment, irreversibly oxidized to sulfinic and sulfonic acids by additional oxidant, condensed with protein or exogenous thiol groups to form disulfide bonds, or directly reduced back to thiols. Sulfenic acids in proteins can act as intermediates in redox catalysis or as critical components in cysteine‚Äźdependent redox regulation.

Keywords: sulfenic acids; cysteine modification; cysteine oxidation; redox regulation; redox catalysis

     
 
GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library

Table of Contents

  • Formation, Reactivity, and Detection of Cysteine Sulfenic Acids in Proteins
  • Functions of Protein Sulfenic Acids
  • Summary
  • Literature Cited
  • Figures
     
 
GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library

Materials

GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library

Figures

Videos

Literature Cited

   Abate, C., Patel, L., Rauscher, III F.J., and Curran, T. 1990. Redox regulation of Fos and Jun DNA‐binding activity in vitro. Science 249:1157‐1161.
   Allison, W.S. 1976. Formation and reactions of sulfenic acids in proteins. Acc. Chem. Res. 9:293‐299.
   Åslund, F., Zheng, M., Beckwith, J., and Storz, G. 1999. Regulation of the OxyR transcription factor by hydrogen peroxide and the cellular thiol‐disulfide status. Proc. Natl. Acad. Sci. U.S.A. 96:6161‐6165.
   Barrett, W.C., DeGnore, J.P., Konig, S., Fales, H.M., Keng, Y.F., Zhang, Z.Y., Yim, M.B., and Chock, P.B. 1999. Regulation of PTP1B via glutathionylation of the active site cysteine 215. Biochemistry 38:6699‐6705.
   Bauer, C.E., Elsen, S., and Bird, T.H. 1999. Mechanisms for redox control of gene expression. Annu. Rev. Microbiol. 53:495‐523.
   Becker, K., Savvides, S.N., Keese, M., Schirmer, R.H., and Karplus, P.A. 1998. Enzyme inactivation through sulfhydryl oxidation by physiologic NO‐carriers. Nat. Struct. Biol. 5:267‐271.
   Boschi‐Muller, S., Assa, S., Sanglier‐Cianferani, S., Talfournier, F., Van Dorsselear, A., and Branlant, G. 2000. A sulfenic acid enzyme intermediate is involved in the catalytic mechanism of peptide methionine sulfoxide reductase from Escherichia coli. J. Biol. Chem. 275:35908‐35913.
   Chen, L., Glover, J.N.M., Hogan, P.G., Rao, A., and Harrison, S.C. 1998a. Structure of the DNA‐binding domains from NFAT, Fos and Jun bound specifically to DNA. Nature 392:42‐48.
   Chen, F., Huang, D.B., and Ghosh, G. 1998b. Crystal structure of p50/p65 heterodimer of transcription factor NF‐kappaB bound to DNA. Nature 391:410‐413.
   Choi, H., Kim, S., Mukhopadhyay, P., Cho, S., Woo, J., Storz, G., and Ryu, S. 2001. Structural basis of the redox switch in the OxyR transcription factor. Cell 105:103‐113.
   Choi, H.‐J., Kang, S.W., Yang, C.‐H., Rhee, S.G., and Ryu, S.‐E. 1998. Crystal structure of a novel human peroxidase enzyme at 2.0 Å resolution. Nat. Struct. Biol. 5:400‐406.
   Claiborne, A., Mallett, T.C., Yeh, J.I., Luba, J., and Parsonage, D. 2001. Structural, redox, and mechanistic parameters for cysteine‐sulfenic acid function in catalysis and regulation. Adv. Prot. Chem. 58:215‐276.
   Conway, M., Poole, L.B., and Huston, S. 2002. Identification of a peroxide‐sensitive redox switch at the CXXC motif in the human mitochondrial branched chain aminotransferase. Biochemistry 41:9070‐9078.
   Costa Seaver, L. and Imlay, J.A. 2001. Alkyl hydroperoxide reductase is the primary scavenger of endogenous hydrogen peroxide in Escherichia coli. J. Bacteriol. 183:7173‐7181.
   DeMaster, E.G., Quast, B.J., Redfern, B., and Nagasawa, H.T. 1995. Reaction of nitric oxide with the free sulfhydryl group of human serum albumin yields a sulfenic acid and nitrous oxide. Biochemistry 34:11494‐11499.
   Denu, J.M. and Tanner, K.G. 1998. Specific and reversible inactivation of protein tyrosine phosphatases by hydrogen peroxide: Evidence for a sulfenic acid intermediate and implications for redox regulation. Biochemistry 37:5633‐5642.
   Denu, J.M. and Tanner, K.G. 2002. Redox regulation of protein tyrosine phosphatases by hydrogen peroxide: Detecting sulfenic acid intermediates and examining reversible inactivation. Methods Enzymol. 348:297‐305.
   Ellis, H.R. and Poole, L.B. 1997a. Roles for the two cysteine residues of AhpC in catalysis of peroxide reduction by alkyl hydroperoxide reductase from Salmonella typhimurium. Biochemistry 36:13349‐13356.
   Ellis, H.R., and Poole, L.B. 1997b. Novel application of 7‐chloro‐4‐nitrobenzo‐2‐oxa‐1,3‐diazole to identify cysteine sulfenic acid in the AhpC component of alkyl hydroperoxide reductase. Biochemistry 36:15013‐15018.
   Finlayson, A.J., MacKenzie, S.L., and Finley, F.W. 1979. Reaction of alanine‐3‐sulfinic acid with 2‐mercaptoethanol. Can. J. Chem. 57:2073‐2077.
   Fuangthong, M., and Helmann, J.D. 2002. The OhrR repressor senses organic hydroperoxides by reversible formation of a cysteine‐sulfenic acid derivative. Proc. Natl. Acad. Sci. U.S.A. 99:6690‐6695.
   Graumann, J., Lilie, H., Tang, X., Tucker, K.A., Hoffmann, J.H., Vijayalakshmi, J., Saper, M., Bardwell, J.C.A., and Jakob, U. 2001. Activation of the redox‐regulated molecular chaperone Hsp33—A two‐step mechanism. Structure 9:377‐387.
   Hegde, R.S., Grossman, S.R., Laimins, L.A., and Sigler, P.B. 1992. Crystal structure at 1.7 Å of the bovine papillomavirus‐1 E2 DNA‐binding domain bound to its DNA target. Nature 359:505‐512.
   Hofmann, B., Hecht, H.‐J., and Flohe, L., 2002. Peroxiredoxins. Biol. Chem. 383:347‐364.
   Hogg, D.R. 1990. Chemistry of sulphenic acids and esters. In The Chemistry of Sulphenic Acids and Their Derivatives (S. Patai, ed.), pp. 361‐402. John Wiley & Sons, New York.
   Ishii, T., Sunami, O., Nakajima, H., Nishio, H., Takeuchi, T., and Hata, F. 1999. Critical role of sulfenic acid formation of thiols in the inactivation of glyceraldehyde‐3‐phosphate dehydrogenase by nitric oxide. Biochem. Pharmacol. 58:133‐143.
   Kim, S.O., Merchant, K., Nudelman, R., Beyer, W.F., Keng, T., DeAngelo, J., Hausladen, A., and Stamler, J.S. 2002. OxyR: A molecular code for redox‐related signaling. Cell 109:383‐396.
   Kratochwil, N.A., Ivanov, A.I., Patriarca, M., Parkinson, J.A., Gouldsworthy, A.M., Murdoch, P.d.S., and Sadler, P.J. 1999. Surprising reactions of Iodo Pt(IV) and Pt(II) complexes with human albumin: Detection of Cys34 sulfenic acid. J. Am. Chem. Soc. 121:8193‐8203.
   Kullik, I., Toledano, M.B., Tartaglia, L.A., and Storz, G. 1995. Mutational analysis of the redox‐sensitive transcriptional regulator OxyR: Regions important for oxidation and transcriptional activation. J. Bacteriol. 177:1275‐1284.
   Lee, S.‐R., Kwon, K.‐S., Kim, S.‐R., and Rhee, S.G. 1998. Reversible inactivation of protein‐tyrosine phosphatase 1B in A431 cells stimulated with epidermal growth factor. J. Biol. Chem. 273:15366‐15372.
   Marnett, L.J., Riggins, J.N., and West, J.D. 2003. Endogenous generation of reactive oxidants and electrophiles and their reactions with DNA and protein. J. Clin. Invest. 111:583‐593.
   McBride, A.A., Klausner, R.D., and Howley, P.M. 1992. Conserved cysteine residue in the DNA‐binding domain of the bovine papillomavirus type 1 E2 protein confers redox regulation of the DNA‐binding activity in vitro. Proc. Natl. Acad. Sci. U.S.A. 89:7531‐7535.
   Mongkolsuk, S., and Helmann, J.D. 2002. Regulation of inducible peroxide stress responses. Mol. Microbiol. 45:9‐15.
   Murakami, T., Nojiri, M., Nakayama, H., Odaka, M., Yohda, M., Dohmae, N., Takio, K., Nagamune, T., and Endo, L. 2000. Post‐translational modification is essential for catalytic activity of nitrile hydratase. Protein Sci. 9:1024‐1030.
   Nagashima, S., Nakasako, M., Dohmae, N., Tsujimura, M., Takio, K., Odaka, M., Yohda, M., Kamiya, N., and Endo, I. 1998. Novel non‐heme iron center of nitrile hydratase with a claw setting of oxygen atoms. Nat. Struct. Biol. 5:347‐351.
   Nakamura, H., Nakamura, K., and Yodoi, J. 1997. Redox regulation of cellular activation. Annu. Rev. Immunol. 15:351‐369.
   Panmanee, W., Vattanaviboon, P., Eiamphungporn, W., Whangsuk, W., Sallabhan, R., and Mongkolsuk, S. 2002. OhrR, a transcription repressor that senses and responds to changes in organic peroxide levels in Xanthomonas campestris pv. phaseoli. Mol. Microbiol. 45:1647‐1654.
   Percival, M.D., Ouellet, M., Campagnolo, C., Claveau, D., and Li, C. 1999. Inhibition of cathepsin K by nitric oxide donors: Evidence for the formation of mixed disulfides and a sulfenic acid. Biochemistry 38:13574‐13583.
   Pineda‐Molina, E., Klatt, P., Vázquez, J., Marina, A., García de Lacoba, M., Pérez‐Sala, D., and Lamas, S. 2001. Glutathionylation of the p50 subunit of NF‐kappaB: A mechanism for redox‐induced inhibition of DNA binding. Biochemistry 40:14134‐14142.
   Poole, L.B. and Claiborne, A. 1989. The non‐flavin redox center of the streptococcal NADH peroxidase. II. Evidence for a stabilized cysteine‐sulfenic acid. J. Biol. Chem. 264:12330‐12338.
   Poole, L.B. and Ellis, H.R. 2002. Identification of cysteine sulfenic acid in AhpC of alkyl hydroperoxide reductase. Methods Enzymol. 348:122‐136.
   Poole, L.B., Karplus, P.A., and Claiborne, A. 2004. Protein sulfenic acids in redox signaling. Annu. Rev. Pharmacol. Toxicol. 44:325‐347.
   Salmeen, A., Andersen, J.N., Myers, M.P., Meng, T.C., Hinks, J.A., Tonks, N.K., and Barford, D. 2003. Redox regulation of protein tyrosine phosphatase 1B involves a sulphenyl‐amide intermediate. Nature 423:769‐773.
   Schmalhausen, E.V., Nagradova, N.K., Boschi‐Muller, S., Branlant, G., and Muronetz, V.I. 1999. Mildly oxidized GAPDH: The coupling of the dehydrogenase and acyl phosphatase activities. FEBS Lett. 452:219‐222.
   Shelton, J.R. and Davis, K.E. 1973. Decomposition of sulfoxides. II. Formation of sulfenic acids. Int. J. Sulfur Chem. 8:205‐216.
   Stamler, J.S., and Hausladen, A. 1998. Oxidative modifications in nitrosative stress. Nat. Struct. Biol. 5:247‐249.
   Storz, G. and Imlay, J.A. 1999. Oxidative stress. Curr. Opin. Microbiol. 2:188‐194.
   Torchinsky, Y.M. 1981. Properties of SH groups. In Sulfur in Proteins (D. Metzler, ed.) pp. 52‐53. Pergamon, Oxford.
   Weissbach, H., Etienne, F., Hoshi, T., Heinemann, S.H., Lowther, W.T., Matthews, B., St. John, G., Nathan, C., and Brot, N. 2002. Peptide methionine sulfoxide reductase: Structure, mechanism of action, and biological function. Arch. Biochem. Biophys. 397:172‐178.
   Wood, Z.A., Schröder, E., Harris, J.R., and Poole, L.B. 2003a. Structure, mechanism and regulation of peroxiredoxins. Trends Biochem. Sci. 28: 32‐40.
   Wood, Z.A., Poole, L.B., and Karplus, P.A. 2003b. Preoxiredoxin evolution and the regulation of hydrogen peroxide signaling. Science 300:650‐653.
   Xanthoudakis, S. and Curran, T. 1996. Redox regulation of AP‐1: Link between transcription factor signaling and DNA repair. Adv. Exp. Med. Biol. 387:69‐75.
   Zheng, M., Åslund, F., and Storz, G. 1998. Activation of the OxyR transcription factor by reversible disulfide bond formation. Science 279:1718‐1721.
Key References
   Claiborne, A., Yeh, J.I., Mallett, T.C., Luba, J., Crane, E.J., 3rd, Charrier, V., and Parsonage, D. 1999. Protein‐sulfenic acids: Diverse roles for an unlikely player in enzyme catalysis and redox regulation. Biochemistry 38:15407‐15416.
  Review of the role of sulfenic acids in proteins.
   Poole and Ellis, 2002. See above.
  Gives practical details about the use of several protocols, including NBD chloride, TNB, and dimedone‐based methods, for identification of sulfenic acids.
   Poole et al., 2004 See above.
  Review of the role of protein sulfenic acids in redox signaling.
GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library