TY - JOUR
T1 - Structural considerations for the rational design of selective anti-trypanosomal agents
T2 - The role of the aromatic clusters at the interface of triosephosphate isomerase dimer
AU - Espinoza-Fonseca, L. Michel
AU - Trujillo-Ferrara, José G.
N1 - Funding Information:
This work was supported, in part, by grants to J.G.T.F. from CONACYT, COFAA-IPN, and CGPI-IPN.
PY - 2005/3/25
Y1 - 2005/3/25
N2 - 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.
AB - 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.
KW - Benzothiazole
KW - Chagas' disease
KW - Docking
KW - Triosephosphate isomerase inhibition
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U2 - 10.1016/j.bbrc.2005.01.043
DO - 10.1016/j.bbrc.2005.01.043
M3 - Article
C2 - 15707966
AN - SCOPUS:13744258061
SN - 0006-291X
VL - 328
SP - 922
EP - 928
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 4
ER -