| Full text | |
| Author(s): |
Solis-Calero, Christian
;
Carvalho, Hernandes F.
Total Authors: 2
|
| Document type: | Journal article |
| Source: | Cell Biology International; v. 41, n. 11, p. 19-pg., 2017-11-01. |
| Abstract | |
Kallikrein 14 (KLK14) is a serine protease linked to several pathologies including prostate cancer and positively correlates with Gleason score. Though KLK14 functioning in cancer is poorly understood, it has been implicated in HGF/Met signaling, given that KLK14 proteolytically inhibits HGF activator-inhibitor 1 (HAI-1), which strongly inhibits pro-HGF activators, thereby contributing to tumor progression. In this work, KLK14 binding to either hepatocyte growth factor activator inhibitor type-1 (HAI-1) or type-2 (HAI-2) was essayed using homology modeling, molecular dynamic simulations and free-energy calculations through MM/PBSA and MM/GBSA. KLK14 was successfully modeled. Calculated free energies suggested higher binding affinity for the KLK14/HAI-1 interaction than for KLK14/HAI-2. This difference in binding affinity is largely explained by the higher stability of the hydrogen-bond networks in KLK14/HAI-1 along the simulation trajectory. A key arginine residue in both HAI-1 and HAI-2 is responsible for their interaction with the S1 pocket in KLK14. Additionally, MM/ GBSA free-energy decomposition postulates that KLK14 Asp174 and Trp196 are hotspots for binding HAI-1 and HAI-2. (AU) | |
| FAPESP's process: | 09/16150-6 - Androgen regulation, sinalization and cellular interactions in prostate development, physiology and regression |
| Grantee: | Hernandes Faustino de Carvalho |
| Support Opportunities: | Research Projects - Thematic Grants |