Sequence divergence of Entamoeba histolytica tubulin is responsible for its altered tertiary structure.
Atypical microtubular structures of the protozoan parasite Entamoeba histolytica (Eh) have been attributed to amino acid sequence divergence of Eh tubulin. To investigate if this sequence divergence leads to significant differences in the tertiary structure of the Eh alphabeta-tubulin heterodimer, we have modeled alphabeta-tubulin heterodimer of Eh based on the crystal structure of mammalian tubulin. The predicted 3D homology model exhibits an overall resemblance with the known crystal structure of mammalian tubulin except for the 16 residue long carboxy terminal region of Eh beta-tubulin. We propose that this C-terminal region may provide steric hindrance in the polymerization of Eh alphabeta-tubulin for microtubule formation. Using docking studies, we have identified the binding sites for different microtubule specific drugs on Eh beta-tubulin. Our model provides a rational framework, both for understanding the contribution of Eh beta-tubulin C-terminal region to alphabeta-tubulin polymerization and design of new anti-protozoan drugs in order to control amoebiasis.
Roy
Debjani
D
Bioinformatics Centre, Bose Institute, Kolkata, India.
Lohia
Anuradha
A
D000595:Amino Acid Sequence; D000818:Animals; D000871:Anthelmintics / Q000737:chemistry / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000378:metabolism; D001542:Benomyl / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D003078:Colchicine / Q000737:chemistry / Q000378:metabolism; D019281:Dimerization; D004748:Entamoeba histolytica / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017239:Paclitaxel / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics; D015800:Protozoan Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D016415:Sequence Alignment; D014404:Tubulin / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism
D000871:Anthelmintics; D000972:Antineoplastic Agents, Phytogenic; D021122:Protein Subunits; D015800:Protozoan Proteins; D014404:Tubulin; D017239:Paclitaxel; D003078:Colchicine; D001542:Benomyl