Homology Modeling And Substrate Docking Study Of Human Glandular Kallikrein 2

As the potential clinical usefulness of human glandular kallikrein 2, it was well studied in recent years. But it's difficult to acquire the crystal structure of hK2, due to its autocatalysis, thus the knowledge of its structure-function relationship is still not clear. In order to exploring this relationship, for further studying and designing new substances, The homology model of hK2 was constructed by homology modeling and optimized by molecular dynamic simulation, finally docked with the known substrate S-2302, for discovering the binding mechanism.The hK2 homology model was reliable after analysis. Its general structural organization was quite similar to other members of kallikrein family. Although, there were appreciable differences observed in the surface loop regain, especially in the kallikrein loop, which may affect the substrate to approach hK2. The active-site triad was highly conserved. The side chain orientation was identical with family members. Also the overall structure of hK2 was stabilized by 5 disulfide bonds that formed by ten conserved Cys residues. The docking study revealed that S1 pocket was similar with hK1, hK4, hK5 and hK6 at some extent. The Arg in substrate P1 was extensively formed hydrogen bond to the residues of bind pocket, thus provide structure foundation of substrate specificity.This work revealed parts of the structure-activity relationship of hK2 and the substrate specificity mechanism. This will be helpful for the further study.