A model for the interaction of paclitaxel with the Bcl-2 loop domain: a chemical approach to induce conformation-dependent phosphorylation.
A homology model for human Bcl-2 was built. Paclitaxel and baccatin III were individually docked into the Bcl-2 loop domain. The conformational space of the loop region on ligand binding was explored by molecular dynamics. The ligand-Bcl-2 interaction energy was calculated by minimization in the binding site. It was found that both paclitaxel's core skeleton and its C-13 side chain contribute significantly to its interaction with Bcl-2. A portion of the Bcl-2 loop domain was found to be locked by the bound paclitaxel and baccatin III in a similar conformation.
Wu
J H
JH
Human Health Research Center, INRS-Institut Armand-Frappier, Université du Quebec, Laval, Canada.
Batist
G
G
Zamir
L O
LO
D000595:Amino Acid Sequence; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry*; D006801:Humans; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017239:Paclitaxel / Q000737:chemistry*; D010766:Phosphorylation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid
D000972:Antineoplastic Agents, Phytogenic; D019253:Proto-Oncogene Proteins c-bcl-2; D017239:Paclitaxel