On the modeling of snake venom serine proteinase interactions with benzamidine-based thrombin inhibitors |
| |
Authors: | Henriques Elsa S Fonseca Nelson Ramos Maria João |
| |
Institution: | REQUIMTE, Departamento de Química, Faculdade de Ciências do Porto, R. Campo Alegre, 687, 4169-007 Porto, Portugal. |
| |
Abstract: | Pit viper venoms contain a number of serine proteinases that exhibit one or more thrombin-like activities on fibrinogen and platelets, this being the case for the kinin-releasing and fibrinogen-clotting KN-BJ from the venom of Bothrops jararaca. A three-dimensional structural model of the KN-BJ2 serine proteinase was built by homology modeling using the snake venom plasminogen activator TSV-PA as a major template and porcine kallikrein as additional structural support. A set of intrinsic buried waters was included in the model and its behavior under dynamic conditions was molecular dynamics simulated, revealing a most interesting similarity pattern to kallikrein. The benzamidine-based thrombin inhibitors alpha-NAPAP, 3-TAPAP, and 4-TAPAP were docked into the refined model, allowing for a more insightful functional characterization of the enzyme and a better understanding of the reported comparatively low affinity of KN-BJ2 toward those inhibitors. |
| |
Keywords: | venom serine proteinase thrombin benzamidine-based inhibitors homology modeling |
本文献已被 PubMed 等数据库收录! |
|