Cerastocytin - Structural Comparison To Thrombin - Hydrophobic Pocket

Hydrophobic Pocket

Cerastocytin contains a hydrophobic domain that binds fibrinopeptide A and in the 3-D confirmation looks very similar to the analogous region of alpha-thrombin. Despite these functional and structural similarities, cerastocytin possesses a distinct amino acid sequence Ile98,Val99, Tyr172, Trp215, which forms the hydrophobic pocket when combined with the 90-loop (Phe90 Val99). The peptides that serve this purpose in thrombin (Leu99, Ile174, Trp215) are known as the aryl binding site and appear to be conserved in many different species.

However, the variation in this sequence within the hydrophobic pocket of cerastocytin suggests that the precise amino acid composition is not relevant to fibrinogen binding ability of the protease, as long as there is a non-polar region to interact with the hydrophobic part of the substrate. On the other hand, the fact that Trp215 is the only residue conserved in thrombinsand cerastocytin suggests the great significance of this one position for fibrinogen cleavage. This is confirmed by the observations of thrombocytin, which lacks the Trp215 residue, participates in platelet aggregation, but not in fibrinogenolytic activity.