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. 2017 Mar 6;8:14574. doi: 10.1038/ncomms14574

Figure 6. AN3661 resistance mutations reside in the MBL and β-CASP domains of PfCSPF3.

Figure 6

(a) Conserved domains predicted by NCBI for PfCPSF3 and its homologues in humans (Hs, gi:18044212), Toxoplasma gondii (Tg, KFG54681.1) and T. thermophilus (Tt, TTHA0252). R, RNA-metabolizing MBL domain. Amino acid numbers are shown for each protein. Asterisks denote amino acids predicted to bind the two zinc atoms in the MBL domain. Amino acids in red were mutated after drug selection. (b) Model of AN3661 (cyan) at the active site of PfCPSF3 (MBL domain, mauve; β-CASP domain, green, RNA-metabolizing MBL domain, orange), built based on the crystal structure of T. thermophilus TTHA0252 (PDB code: 3IEM). Residues D470, Y408, T409 and T406, which were mutated after selection by AN3661, are shown as blue stick models. The negatively charged benzoxaborole group interacts extensively with the two catalytic zinc ions (grey), and the carboxylate side chain interacts with R290 and Y252, forming a salt bridge and hydrogen bond, respectively.