Hirudin: Structure, Function, and Inhibition

ADVANCED PHYSICAL CHEMISTRY
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Hirudin
Abstract
It refers to a peptide that occurs naturally in the salivary glands of the blood-sucking leeches.
The examples of such blood leeches include Hirudin medicinalis which is known to be
having blood anticoagulant property. This property is very crucial for the alimentary habit of
the hematophagy shown by the leeches considering that it keeps the blood flowing after the
first operation of the phlebotomy is carried out on the skin of the host by the worm (Sellers
et.al 2014).
Structure
During the times of the great scientists John Berry, there were publications of the paper that
dealing with the coagulation of the blood. In his work, he discovered that the leech secreted a
very powerful anticoagulant and he refers to the anticoagulant as the hirudin. The isolation of
this structure was not done until the year 1950 with the determination of its full structure
being finished on the year 1976.The full length of this structure is made up of roughly 65
amino acids.
The present amino acids are arranged in the form of a solid N-terminal domain possessing
three disulphide bonds and a terminal of C. The C compound is perfectly disordered when the
protein is subjected to the uncompleted solution. The residues of the amino acids normally
form a parallel beta strand of 1-3 to the residues of thrombin 214-217.The ser-195 O gamma
atom present in the site of the catalytic will form the hydrogen bond with the nitrogen atom
of the residue 1. There are several electrostatic interactions between the C-terminal domain
and the anion-binding of the thrombin exosite (Lu et.ai 2013)
The last five residues form a loop that is helical and this results into hydrophobic contacts.
There are several mixtures of the isoforms of the protein in the natural Rudin. The

homogeneous preparation of the hirudin can be an achieved using a technique of the
recombinant.
Figure 1: Structure of hirudin extracted from Yingxin et.al 2014
In the final stages of the coagulation of the blood, the most common activity is the conversion
of the fibrinogen into the fibrin. This is done by an enzyme called serine protease thrombin.
The production of the thrombin is from the prothrombin and this is facilitated by an enzyme
called prothrombinase towards the end of the coagulation stages.
The activity includes the use of the Factor Xa together with the Factor Va as the cofactor
especially in the final stages of the coagulation. A blood clot is formed through linking of the
fibrin by the factor XIII. The XIII is also known as the fibrin stabilizing factor. The primary
inhibitor of the thrombin in the normal circulation of the blood is the antithrombin. The
anticoagulant activity of the hirudin is based on its capability to inhibit the activity of the
thrombin of procoagulation. This is what makes it similar to the antithrombin.
Hirudin is the primary natural inhibitor of the thrombin. It normally binds to and inhibit only
the thrombin that ha been activated. This limits its activities to specifically on the
fibrinogen’s hirudin therefore prevents the formation of the clots and the thrombi. This makes
the activity to be a thrombolytic.