Structural comparison of the interaction of tubulin with various ligands affecting microtubule dynamics

• Published in: Current cancer drug targets Vol. 12; no. 6; p. 658
• Main Authors: Stec-Martyna, E, Ponassi, M, Miele, M, Parodi, S, Felli, L, Rosano, C
• Format: Journal Article
• Language: English
• Published: Netherlands 01.07.2012
• Subjects: Animals; Antineoplastic Agents - chemistry; Antineoplastic Agents - metabolism; Antineoplastic Agents - pharmacology; Binding Sites; Crystallography, X-Ray; Drug Design; Humans; Ligands; Magnetic Resonance Spectroscopy; Microtubules - chemistry; Microtubules - drug effects; Microtubules - metabolism; Models, Molecular; Molecular Structure; Protein Conformation; Protein Structure, Tertiary; Structure-Activity Relationship; Tubulin - chemistry; Tubulin - drug effects; Tubulin - metabolism; Tubulin Modulators - chemistry; Tubulin Modulators - metabolism; Tubulin Modulators - pharmacology
• ISSN: 1873-5576
• DOI: 10.2174/156800912801784893

Microtubules (MTs), which are highly dynamic assemblies of the protein tubulin, play important and diverse roles in eukaryotic cells. MT dynamics are regulated during the cell cycle by interacting with a large number of endogenous cellular regulators. In addition, many anti-tumour drugs and natural ligands that interact directly with tubulin are able to either stabilise or destabilise MTs and to disrupt the normal dynamics. Herein, we compare the structures of tubulin when complexed with different ligands in order to analyse: (i) various binding-sites of the protein and different positions of ligands within the microtubule (ii) the diverse effect on the microtubule dynamics. The structures and data given are essential for understanding tubulin-ligand interactions and their influence on the regulation of the microtubule system.