← Back to Search
Modeling The Yew Tree Tubulin And A Comparison Of Its Interaction With Paclitaxel To Human Tubulin
J. Tuszynski, T. Craddock, Jonathan Y. Mane, K. Barakat, C. Tseng, M. Gajewski, P. Winter, L. Alisaraie, Jordan Patterson, E. Carpenter, Weiwei Wang, M. Deyholos, Linji Li, Xiao Sun, Y. Zhang, G. Wong
Published 2012 · Biology, Medicine
Save to my Library
Download via 🐼 PaperPanda Download via oaDOI Download via OAB Download via LibKey Download via Google Google ScholarAnalyze on Scholarcy Visualize in Litmaps
Reduce the time it takes to create your bibliography by a factor of 10 by using the world’s favourite reference manager
Time to take this seriously.
ABSTRACTPurposeTo 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.MethodsTubulin 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.ResultsWe 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.ConclusionsThe 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.
This paper references
Plant antitumor agents. VI. The isolation and structure of taxol, a novel antileukemic and antitumor agent from Taxus brevifolia.
M. Wani (1971)
The Protein Data Bank: a computer-based archival file for macromolecular structures.
F. Bernstein (1977)
Taxol stabilizes microtubules in mouse fibroblast cells.
P. Schiff (1980)
The neighbor-joining method: a new method for reconstructing phylogenetic trees.
N. Saitou (1987)
PHYLIP—phylogeny inference package (version 3.2)
J. Felsenstein (1989)
Basic local alignment search tool.
S. Altschul (1990)
The rapid generation of mutation data matrices from protein sequences
David T. Jones (1992)
Comparative protein modelling by satisfaction of spatial restraints.
A. Sali (1993)
PROCHECK: a program to check the stereochemical quality of protein structures
R. Laskowski (1993)
Comparative protein modeling by satisfaction of spatial restraints
Andrej ⩽ali (1995)
Structure of the alpha beta tubulin dimer by electron crystallography.
E. Nogales (1998)
Multiple forms of tubulin: different gene products and covalent modifications.
R. Luduena (1998)
Changes in Microtubule Protofilament Number Induced by Taxol Binding to an Easily Accessible Site
J. F. Díaz (1998)
NAMD2: Greater Scalability for Parallel Molecular Dynamics
L. Kalé (1999)
NAMD 2 : greater scalability for parallel molecular dynam
L Kalé (1999)
Calculating structures and free energies of complex molecules: combining molecular mechanics and continuum models.
P. Kollman (2000)
EMBOSS: the European Molecular Biology Open Software Suite.
P. Rice (2000)
Electrostatics of nanosystems: Application to microtubules and the ribosome
Nathan A. Baker (2001)
Refined structure of alpha beta-tubulin at 3.5 A resolution.
J. Löwe (2001)
Estimates of lateral and longitudinal bond energies within the microtubule lattice
Vincent VanBuren (2002)
Microtubule structure at 8 A resolution.
H. Li (2002)
PyMOL Release 0.99
W. DeLano (2002)
Mobility of taxol in microtubule bundles.
J. Ross (2003)
The physical basis of microtubule structure and stability
D. Sept (2003)
Fast Kinetics of Taxol Binding to Microtubules
J. F. Díaz (2003)
Nordihydroguaiaretic Acid, of a New Family of Microtubule-stabilizing Agents, Shows Effects Differentiated from Paclitaxel
M. Nakamura (2003)
Microtubule alterations and mutations induced by desoxyepothilone B: implications for drug-target interactions.
N. Verrills (2003)
PDB2PQR: an automated pipeline for the setup of Poisson-Boltzmann electrostatics calculations
Todd J. Dolinsky (2004)
Development and testing of a general amber force field
Junmei Wang (2004)
Scalable molecular dynamics with NAMD
James C. Phillips (2005)
Macromolecular Accessibility of Fluorescent Taxoids Bound at a Paclitaxel Binding Site in the Microtubule Surface*
J. F. Díaz (2005)
Anticancer Agents from Natural Products
G. Cragg (2005)
D. Benson (2005)
Comparative modelling of human β tubulin isotypes and implications for drug binding.
J. Torin Huzil (2006)
Paclitaxel-resistant cells have a mutation in the paclitaxel-binding region of β-tubulin (Asp26Glu) and less stable microtubules
Malathi Hari (2006)
Insights into the mechanism of microtubule stabilization by Taxol
Hui Xiao (2006)
Comparison of multiple Amber force fields and development of improved protein backbone parameters
V. Hornak (2006)
Clustal W and Clustal X version 2.0
Mark A. Larkin (2007)
Interactive Tree Of Life (iTOL): an online tool for phylogenetic tree display and annotation
I. Letunic (2007)
Cyclostreptin binds covalently to microtubule pores and lumenal taxoid binding sites.
R. M. Buey (2007)
PDB2PQR: expanding and upgrading automated preparation of biomolecular structures for molecular simulations
Todd J. Dolinsky (2007)
ClustalW and Clustal X version 2 . 0
M Larkin (2007)
Taxol allosterically alters the dynamics of the tubulin dimer and increases the flexibility of microtubules.
A. Mitra (2008)
The Isotypes of Tubulin
R. Luduena (2008)
The role of microtubules in cell biology, neurobiology, and oncology /
A. Fojo (2008)
The isotypes of tubulin In: Fojo T, editor. The role of microtubules in cell biology, neurobiology, and oncology. Totowa: Humana
Rf Ludueña (2008)
Identification and Characterization of an Intermediate Taxol Binding Site Within Microtubule Nanopores and a Mechanism for Tubulin Isotype Binding Selectivity
Holly Freedman (2009)
Interactive Tree Of Life v2: online annotation and display of phylogenetic trees made easy
I. Letunic (2011)
Full-length transcriptome assembly from RNA-Seq data without a reference genome.
M. Grabherr (2011)
Anticancer Agents from Natural Products, Second Edition
D. Cragg (2011)
A transposase strategy for creating libraries of circularly permuted proteins
Manan M. Mehta (2012)
Reorganizing the protein space at the Universal Protein Resource (UniProt)
The UniProt Consortium (2012)
GenBank. Nucleic Acids Res
Da Benson (2012)
The Alberta 1000 Plants Initiative (Alberta Advanced Education and Technology, Musea Ventures, BGI-Shenzhen, Alberta iCORE, to Wong GKS) Available from
This paper is referenced by
C-terminal Tail of β-Tubulin and its Role in the Alterations of Dynein Binding Mode
K. Heale (2020)
Tracing chirality, diameter dependence, and temperature-controlling of single-walled carbon nanotube non-covalent functionalization by biologically compatible peptide: insights from molecular dynamics simulations
Leila Tohidifar (2019)
Natural products used as a chemical library for protein-protein interaction targeted drug discovery.
Xuemei Jin (2018)
Drug metabolites and their effects on the development of adverse reactions: Revisiting Lipinski’s Rule of Five
C. M. Chagas (2018)
Modeling the Colchicum autumnale Tubulin and a Comparison of Its Interaction with Colchicine to Human Tubulin
Ivana Spasevska (2017)
Microtubules dual chemo- and thermo-responsive depolymerization & optimization of noncovalent loading of vinblastine on single-walled carbon nanotube
Z. Li (2016)
New design of nucleotide excision repair (NER) inhibitors for combination cancer therapy.
Francesco Gentile (2016)
Target fishing: a key to unlock the One-To-Many puzzle in drug discovery
A. Ganesan (2016)
Molecular Dynamics Studies for Optimization of Noncovalent Loading of Vinblastine on Single-Walled Carbon Nanotube
Z. Li (2016)
Identification of okadaic acid binding protein 2 in reconstituted sponge cell clusters from Halichondria okadai and its contribution to the detoxification of okadaic acid.
K. Konoki (2015)
Human PD-1 binds differently to its human ligands: a comprehensive modeling study.
Clement Viricel (2015)
High-throughput Screening of New Antimitotic Compounds Based on Potential of Virtual Organization CSLabGrid
Pavel A Karpov (2015)
High-Throughput Screening of New Antimitotic Compounds Based on CSLabGrid Virtual Organization
P. Karpov (2015)
Elucidating the Mechanism of Action of the Clinically Approved Taxanes: A Comprehensive Comparison of Local and Allosteric Effects
Cassandra D M Churchill (2015)
Modelling Off-target Interactions (I): Cardiotoxicity
K. Barakat (2015)
Baby Steps Toward Modelling The Full human Programmed Death-1 (PD-1) Pathway
Marawan Ahmed (2015)
Entropy in bimolecular simulations: A comprehensive review of atomic fluctuations-based methods.
S. Kassem (2015)
Expression of recombinant alpha and beta tubulins from the yew Taxus cuspidata and analysis of the microtubule assembly in the presence of taxol
Yuma Kudo (2014)
Microtubule drugs: action, selectivity, and resistance across the kingdoms of life
V. Dostál (2014)
Tubulin-interactive stilbene derivatives as anticancer agents
R. Mikstacka (2013)
Microtubule-active drugs: mechanism of action and resistance Mikrotubulární jedy: mechanismus účinku a rezistence