Thrombin

Thrombin plays several roles in coagulation. It has been an attractive target for rational drug design efforts. There are two major inhibitor binding sites. The active site is the obvious one, but X-ray crystallography showed that the leech anticoagulant hirudin binds to another region called the exosite.

This crystal structure shows thrombin (activated by cleavage into heavy & light chains) with hirugen bound into the exosite and another inhibitor bound into the active site.

• Blue = Thrombin heavy chain (16-245)
• Magenta = Active site triad (His57, Asp102, Ser195)
• Orange = Asp189 in specificity pocket. The negative charge on the Asp sidechain normally interacts with a positively charged arginine sidechain of the substrate.
• Green = Hirugen
• Spacefill = Active site inhibitor, a potential antithrombotic drug.

• Blue = Thrombin heavy chain (16-245)
• Magenta = Active site triad (His57, Asp102, Ser195)
• Orange = Asp189 in specificity pocket. The negative charge on the Asp sidechain normally interacts with a positively charged arginine sidechain of the substrate.
• Green = Hirugen
• Spacefill = Active site inhibitor, a potential antithrombotic drug.