L-2-Thiohistidine (also named 2-mercapto-L-histidine or L-2-thiolhistidine) is a 2-thioimidazole analog of L-histidine. The 2-thioimidazole structure has been found as a post-translational modification of copper proteins, such as molluskan hemocyanin and fungal tyrosinase, in the vicinity of the copper ion that is coordinated at the active site of these proteins [1-5].
Stable towards oxygen, L-2-thiohistidine is an efficient antioxidant through its ability to chelate divalent metallic cations, such as Cu2+ and Zn2+ [6,7], and to prevent from singlet oxygen formation [8], a strong oxidizing agent involved in UVA-induced skin damage. This supports the protective effect of L-2-thiohistidine that has been reported in studying the photochemical inactivation of various enzymes [9-11].



  1. Primary structure of tyrosinase from Neurospora crassa. II. Complete amino acid sequence and chemical structure of a tripeptide containing an unusual thioether – LERCH K. – 1982 – J. Biol. Chem., 257(11):6414-6419
  2. Evidence for a cysteine-histidine thioether bridge in functionnal units of molluscan haemocyanins and location of the disulfide bridges in functional units d and g of the βc-haemocyanin of Helix pomatia – GIELENS C., DE GEEST N., XIN X.Q., DEVREESE B., VAN BEEUMEN J., and PRÉAUX G. – 1997 – Eur. J. Biochem., 248(3):879-888
  3. Chemically modified amino acids in copper proteins that bind or activate dioxygen – HALCROW M.A. – 2001 – Angew. Chem. Int. Ed., 40(2):346-349
  4. Geometric preferences of crosslinked protein-derived cofactors reveal a high propensy for near-sequence pairs – SWAIN M.D., and BENSON D.E. – 2005 – Prot. Struct. Funct. Bioinf., 59(1):64-71
  5. Conformational stabilization at the active site of molluskan (Rapana thomasiana) hemocyanin by a cysteine–histidine thioether bridge: A study by mass spectrometry and molecular modeling – GIELENS C., IDAKIEVA K., DE MAEYER M., VAN DEN BERGH V., SIDDIQUI N.I., and COMPERNOLLE F. – 2007 – Peptides, 28(4):790-797
  6. Inhibition of urocanase by cupric ion – HUG D.H., and ROTH D. K. – 1973 – Biochim. Biophys. Acta, 293(2):497-505
  7. Physico-chemical and metal-binding properties of thiolhistidine – TAKESHIMA S., and SAKURAI H. – 1982 – Inorg. Chim. Acta, vol. 66, pp. 119-124
  8. Some prevalent biomolecules as defenses against singlet oxygen damage – DAHL T.A., ROBERT MIDDEN X., and HARTMAN P.E. – 1988 – Photochem. Photobiol., vol. 47(3):357-362
  9. Oxidation, photosensitized by certain diketones, of enzymes and protection against such oxidation by histidine derivatives – MÄKINEN K.K., and MÄKINEN P.L. – 1982 – Biosc. Rep., 2(3):169-175
  10. Photochemical inactivation of Aeromonas aminopeptidase by 2,3-butanedione – MÄKINEN K.K., MÄKINEN P.L., WILKES S.H., BAYLISS M.E., and PRESCOTT J.M. – 1982 – J. Biol. Chem., 257(4):1765-1772
  11. Photochemical inactivation of lactoperoxidase sensitized by carbonyl compounds – MÄKINEN K.K., and MÄKINEN P.L. – 1982 – Eur. J. Biochem., 123(1):171-178