Inhibitory mechanism of daphnodorins for human chymase

We investigated the inhibitory mechanisms of daphnodorins for human chymase using three dimensional molecular modeling. In daphnodorin A-human chymase complex, daphnodorin A was fixed to the active site via hydrogen bonds wit h Ala177, Phe29, and Gly199 in human chymase, and it formed hydrogen bonds with Ser182 and Gly180, and this complex was formed stably. In daphnodorin B-human chymase complex, daphnodorin B formed hydrogen bonds with Lys28 and Phe29 in human chymase, but it could not form hydrogen bonds with Gly199, Ala177, and Lys179. The phenyl group of daphnodorin B shifted from the P1 h ole in human chymase in comparison with that of daphnodorin A. For the inhi bition of human chymase by daphnodorins, we indicated that it was significa nt whether daphnodorins formed hydrogen bonds with Ala177 located in the P1 hole, Ser182 located in the active site, Gly180 located in the anion hole, and with Gly199, Phe29, and Lys28 in human chymase. (C) 2001 Academic Pres s.