Differential colchicine-binding across eukaryotic families: the role of highly conserved Pro268beta and Ala248beta residues in animal tubulin.
Colchicine-tubulin interaction, responsible for the disruption of microtubule formation, has immense pharmacological importance but is poorly understood in terms of its biological significance. The interaction is characterized by a marked higher affinity of colchicine for animal tubulins compared to tubulins from plants, fungi and protists. From an analysis of tubulin sequences and colchicine-tubulin crystal structure, we propose that Pro268beta and Ala248beta (270beta and 250beta in the crystal structure 1SA0) in animal tubulin are crucial for the observed differential binding. We also suggest that mediated by the binding of endogenous molecules to the colchicine-binding site, microtubule assembly in eukaryotes may be modulated in a family specific manner.
Banerjee
Mithu
M
Department of Biochemistry, Bose Institute, P-1/12 CIT Scheme VIIM, Kolkata 700 054, India.
Roy
Debjani
D
Bhattacharyya
B
B
Basu
Gautam
G
D000409:Alanine / Q000737:chemistry / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D003078:Colchicine / Q000737:chemistry*; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D008969:Molecular Sequence Data; D009154:Mutation; D011392:Proline / Q000737:chemistry / Q000235:genetics; D011487:Protein Conformation; D014404:Tubulin / Q000737:chemistry* / Q000235:genetics
D014404:Tubulin; D011392:Proline; D000409:Alanine; D003078:Colchicine