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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Modeling the yew tree tubulin and a comparison of its interaction with paclitaxel to human tubulin
Pharmaceutical Research, Volume 29, No. 11, Year 2012
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Description
Purpose: To explore possible ways in which yew tree tubulin is naturally resistant to paclitaxel. While the yew produces a potent cytotoxin, paclitaxel, it is immune to paclitaxel's cytotoxic action. Methods: Tubulin sequence data for plant species were obtained from Alberta 1000 Plants Initiative. Sequences were assembled with Trinity de novo assembly program and tubulin identified. Homology modeling using MODELLER software was done to generate structures for yew tubulin. Molecular dynamics simulations and molecular mechanics Poisson-Boltzmann calculations were performed with the Amber package to determine binding affinity of paclitaxel to yew tubulin. ClustalW2 program and PHYLIP package were used to perform phylogenetic analysis on plant tubulin sequences. Results: We specifically analyzed several important regions in tubulin structure: the high-affinity paclitaxel binding site, as well as the intermediate binding site and microtubule nanopores. Our analysis indicates that the high-affinity binding site contains several substitutions compared to human tubulin, all of which reduce the binding energy of paclitaxel. Conclusions: The yew has achieved a significant reduction of paclitaxel's affinity for its tubulin by utilizing several specific residue changes in the binding pocket for paclitaxel. © 2012 Springer Science+Business Media, LLC.
Authors & Co-Authors
Tuszynski, J. A.
Canada, Edmonton
University of Alberta
Canada, Edmonton
Cross Cancer Institute
Craddock, Travis J.A.
Canada, Edmonton
University of Alberta
Mane, Jonathan Y.
Canada, Edmonton
University of Alberta
Barakat, Khaled H.
Canada, Edmonton
University of Alberta
Egypt, Fayoum
Fayoum University
Tseng, Chih Yuan
Canada, Edmonton
University of Alberta
Gajewski, Melissa
Canada, Edmonton
University of Alberta
Winter, Philip
Canada, Edmonton
University of Alberta
Alisaraie, Laleh
Canada, Edmonton
University of Alberta
Patterson, Jordan
Canada, Edmonton
University of Alberta
Carpenter, Eric J.
Canada, Edmonton
University of Alberta
Wang, Weiwei
Canada, Edmonton
University of Alberta
Deyholos, Michael K.
Canada, Edmonton
University of Alberta
Li, Linji
China, Shenzhen
Bgi-shenzhen
Sun, Xiao
China, Shenzhen
Bgi-shenzhen
Zhang, Yong
China, Shenzhen
Bgi-shenzhen
Wong, Gane Ka Shu
Canada, Edmonton
University of Alberta
China, Shenzhen
Bgi-shenzhen
Statistics
Citations: 16
Authors: 16
Affiliations: 4
Identifiers
Doi:
10.1007/s11095-012-0829-y
ISSN:
07248741
e-ISSN:
1573904X