Primary structure and function of novel O-glycosylated hirudins from the leech Hirudinaria manillensis.
Comparative study published in Biochemistry (1992)
Abstract
Hirudin from the leech Hirudo medicinalis is a most powerful anticoagulant, and many isoforms have been described. In the present work, the primary structure of two hirudins from the leech Hirudinaria manillensis has been elucidated. The antithrombotic activity is similar to that of H. medicinalis hirudins although the sequence identity is below 60%. Surprisingly, the hirudins were found to be glycosylated at one site. Sugar analysis after methanolysis yielded fucose, galactose, and N-acetylgalactosamine. These results combined with data from matrix-assisted laser desorption ionization mass spectrometry, plasma desorption mass spectrometry, capillary zone electrophoresis, and lectin-binding tests indicate that the sequence is Fuc-Gal beta 1-3GalNAc-(O-threonine). This structure shows an interesting similarity to human blood group H determinants.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Summary
Hirudin from the leech Hirudo medicinalis is a most powerful anticoagulant, and many isoforms have been described. In the present work, the primary structure of two hirudins from the leech Hirudinaria manillensis has been elucidated.
Why This Matters for Hirudotherapy
This comparative biochemistry study elucidated the primary structure of two hirudins from the leech Hirudinaria manillensis and found their antithrombotic activity similar to that of Hirudo medicinalis hirudins despite under 60% sequence identity, and unexpectedly showed these hirudins are glycosylated at a single site (Fuc-Gal beta1-3GalNAc on threonine), a structure the authors note resembles human blood-group H determinants. This matters to the leech-secretome story because it documents that potent thrombin-directed anticoagulants are not unique to Hirudo medicinalis but recur across leech species, and it adds a post-translational (glycosylation) dimension to hirudin diversity relevant to understanding and engineering these molecules. As an in-vitro structural and functional characterization it speaks to molecular pharmacology, not to clinical outcomes of hirudotherapy, and the antithrombotic comparison was made at the biochemical level rather than in patients.
Citation
Primary structure and function of novel O-glycosylated hirudins from the leech Hirudinaria manillensis.
Steiner V et al. · Biochemistry, 1992
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