Tyrosine-O-sulfation is a widespread affinity enhancer among thrombin interactors
Structural biology published in Biochemical Society Transactions (2022)
Abstract
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.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Summary
Review of tyrosine-O-sulfation as broad affinity enhancer for thrombin interactors including hirudin — key structural biology for leech-derived inhibitor design.
Why This Matters for Hirudotherapy
This article discusses tyrosine-O-sulfation as a post-translational modification associated with the modulation of protein-protein interactions in several physiological processes, including hemostasis, with specific attention to thrombin-directed anticoagulants. It notes that hirudin, a potent thrombin inhibitor from Hirudo medicinalis, undergoes tyrosine-O-sulfation, and that the discovery of hirudin led to clinically applied leech-inspired analogs. The abstract states that tyrosine-O-sulfation has been shown to enhance the anticoagulant properties of peptides from ticks, mosquitos, and flies, and that some of these molecules mimic thrombin's substrates. For ASH's domain, this work contextualizes hirudin within a broader landscape of thrombin inhibitors and PTM-mediated affinity enhancement, though the abstract does not explicitly attribute enhanced potency to sulfated hirudin itself and does not specify the study design.
Citation
Tyrosine-O-sulfation is a widespread affinity enhancer among thrombin interactors.
Ripoll-Rozada J et al. · Biochemical Society transactions, 2022
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