Hirudin

Hirudin
crystallographic analysis at 3.0-angstroms resolution of the binding to human thrombin of four active site-directed inhibitors
Identifiers
Symbol	Hirudin
Pfam	PF00713
InterPro	IPR000429
SCOP	4htc
SUPERFAMILY	4htc
Available protein structures: Pfam structures PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Hirudin is a naturally occurring peptide in the salivary glands of medicinal leeches (such as Hirudo medicinalis) that has a blood anticoagulant property. This is fundamental for the leeches’ alimentary habit of hematophagy, since it keeps the blood flowing after the initial phlebotomy performed by the worm on the host’s skin.

During his years in Birmingham and Edinburgh, John Berry Haycraft had been actively engaged in research and published papers on the coagulation of blood, and in 1884, he discovered that the leech secreted a powerful anticoagulant, which he named hirudin, although it was not isolated until the 1950s, nor its structure fully determined until 1976. Full length hirudin is made up of 65 amino acids. These amino acids are organized into a compact N-terminal domain containing three disulfide bonds and a C-terminal domain that is completely disordered when the protein is un-complexed in solution.Amino acid residues 1-3 form a parallel beta- strand with residues 214-217 of thrombin, the nitrogen atom of residue 1 making a hydrogen bond with the Ser-195 O gamma atom of the catalytic site. The C-terminal domain makes numerous electrostatic interactions with an anion-binding exosite of thrombin, while the last five residues are in a helical loop that forms many hydrophobic contacts. Natural hirudin contains a mixture of various isoforms of the protein. However, recombinant techniques can be used to produce homogeneous preparations of hirudin.