Tyrosine-O-sulfation is a widespread affinity enhancer among thrombin interactors

Biochem Soc Trans. 2022 Feb 28;50(1):387-401. doi: 10.1042/BST20210600.


Tyrosine-O-sulfation is a common post-translational modification (PTM) of proteins following the cellular secretory pathway. First described in human fibrinogen, tyrosine-O-sulfation has long been associated with the modulation of protein-protein interactions in several physiological processes. A number of relevant interactions for hemostasis are largely dictated by this PTM, many of which involving the serine proteinase thrombin (FIIa), a central player in the blood-clotting cascade. Tyrosine sulfation is not limited to endogenous FIIa ligands and has also been found in hirudin, a well-known and potent thrombin inhibitor from the medicinal leech, Hirudo medicinalis. The discovery of hirudin led to successful clinical application of analogs of leech-inspired molecules, but also unveiled several other natural thrombin-directed anticoagulant molecules, many of which undergo tyrosine-O-sulfation. The presence of this PTM has been shown to enhance the anticoagulant properties of these peptides from a range of blood-feeding organisms, including ticks, mosquitos and flies. Interestingly, some of these molecules display mechanisms of action that mimic those of thrombin's bona fide substrates.

Keywords: anticoagulant; blood clotting; post translational modification; thrombin inhibitor; tyrosine sulfation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Anticoagulants
  • Hirudins* / chemistry
  • Hirudins* / metabolism
  • Hirudins* / pharmacology
  • Thrombin* / metabolism
  • Tyrosine / metabolism


  • Anticoagulants
  • Hirudins
  • Tyrosine
  • Thrombin