Phylogeny and sequence alignment.

<p>(<b>A</b>) Phylogenetic analysis of <i>Pf</i>ABCB2 (<i>Pf</i>MDR2) and <i>Pf</i>ABCB6 (<i>Pf</i>MDR6) (sequences in <b><a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1012593#ppat.1012593.s010" target="_blank">S1 Table</a></b>). LG+R+F model was found to be the best substitution model predetermined by ATGC: SMS (Smart model selection) in PhyML 3. 0, visualised by iTOL software. Bootstrap support values (in red) and branch lengths of the unrooted tree are shown. Green arrow indicates a more recent common ancestor shared between <i>Pf</i>ABCB2 (<i>Pf</i>MDR2) and eukaryotic HMTs. (<b>B</b>) Multiple sequence alignment of ATM1 homologs from apicomplexan parasites. ClustalW alignment of ATM1- like proteins of <i>P</i>. <i>falciparum</i>, <i>Toxoplasma gondii</i> and <i>Cryptosporidium parvum</i> with <i>Saccharomyces cerevisiae</i> ATM1, bacterial ATM1 of <i>Novosphingobium aromaticivorans</i>, fungal ATM1 of <i>Chaetomium thermophilum</i>, ATM3 (ABCB25) of <i>Arabidopsis thaliana</i>, and human ABCB7. The NTE, transmembrane region, insertion and CTD with conserved ATP-binding sites are indicated. Positions showing the extent of full-length recombinant <i>Pf</i>ATM1 (FL) and its CTD and NTE domains are marked. Black arrows and blue circles indicate GSSG binding sites in <i>Na</i>ATM1 and GSH binding sites in <i>Sc</i>ATM1, respectively. [2Fe-2S]GS<sub>4</sub> cluster coordination sites in <i>Sc</i>ATM1 and <i>Hs</i>ABCB7 are marked by grey and orange circles, respectively. Gatekeeper residues in <i>Na</i>ATM1, <i>Ct</i>ATM1 and <i>Pf</i>ATM1 are boxed in blue. The TM6 helix of <i>Na</i>ATM1 is indicated by a blue dashed line. The predicted α-helix (PSIPRED prediction) in the NTE of <i>Pf</i>ATM1 is shown by a red line and the hydrophobic stretch in this region is indicated by a green dashed line. Poly(Asn) in the NTE is indicated by a blue line.</p> <p>(PDF)</p>