Structural considerations for the rational design of selective anti-trypanosomal agents: The role of the aromatic clusters at the interface of triosephosphate isomerase dimer

L. Michel Espinoza-Fonseca, José G. Trujillo-Ferrara

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21 Scopus citations

Abstract

Seven benzothiazoles were successfully docked into the interface of both human and trypanosomal triosephosphate isomerases, and the binding free energies of each complex were calculated using the program AutoDock. Structural and energetical analysis of the complexes showed that large benzothiazoles could form more stable complexes with trypanosomal triosephosphate isomerase than with human triosephosphate isomerase. Thus, we hypothesize that the distribution of the residues forming the aromatic clusters at the enzyme's interface and the size of the inhibitors might play a crucial role in the selective inhibition of TcTIM. Following the findings here presented, it is possible to better determine the structural elements involved in the origin of the selectivity at the trypanosomal triosephosphate isomerase interface, and to enable efficient anti-trypanosomal drug design strategies.

Original languageEnglish (US)
Pages (from-to)922-928
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume328
Issue number4
DOIs
StatePublished - Mar 25 2005

Bibliographical note

Funding Information:
This work was supported, in part, by grants to J.G.T.F. from CONACYT, COFAA-IPN, and CGPI-IPN.

Keywords

  • Benzothiazole
  • Chagas' disease
  • Docking
  • Triosephosphate isomerase inhibition

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