FIGURE 5.

Predicted topology of CfNT2 TM4. A, alignment of protozoan and human ENT proteins around predicted TM4. The filled arrowheads indicate residues in CfNT2 shown by SCAM to be water-accessible; the open arrowhead indicates Lys¹⁵⁵, which influences ligand specificity. The line below the alignment indicates a published prediction for the residues included in TM4 in human transporters hENT1 and hENT2 (11), which is consistent with these results. The line above the alignment indicates a previous prediction for the topology of CfNT2 TM4 (17). GenBank^TM accession numbers are as follows: CfNT2 (AAG22611), LdNT2 (AAF74264), LdNT1.1 (AAC32597), TbNT2 (AAF04490), TbAT1 (AAB93848), hENT1 (AAC51103), hENT2 (NP_001523). The GeneDB accession number for LmajNT3 is LmjF13.1210. B, helical wheel diagram of residues 151–170 from CfNT2. Positions that were observably modified with MTSEA and/or MTSES in the SCAM analysis are highlighted in gray. Those whose modification could be partially blocked by the presence of ligand are highlighted in black.