Fig. 5: Structure–activity relationship of the CTCB allosteric inhibitors and binding interaction of the lead CTCB series. | Nature Communications

Fig. 5: Structure–activity relationship of the CTCB allosteric inhibitors and binding interaction of the lead CTCB series.

From: Fast acting allosteric phosphofructokinase inhibitors block trypanosome glycolysis and cure acute African trypanosomiasis in mice

Fig. 5

a Structure–activity of the pyrrolopyridine scaffold. Three regions in the structure are highlighted in green, blue and yellow, and the respective biological properties or activities are indicated. b X-ray structure of CTCB-405 bound to TbPFK showing three binding features of the pyrrolopyridine lead series. The chlorine atom forms a ‘halogen bond’ with the backbone carbonyl atom from Gly (Cl…O = 3.3 Å). There is an unusual short attractive interaction between the carboxyl oxygen atom of Asp199 and the amide carbon atom of CTCB-405 (O…C = 3.1 Å). The ethylamine side chain adopts a conformation allowing salt bridge formation with Asp199 (N…O = 2.6 Å).

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