2.A.40.4.3
The YgfO (XanQ) purine (xanthine) transporter. Residues involved in substrate binding have been identified (Georgopoulou et al., 2010). TMS3 functions in substrate recognition (Karena and Frillingos, 2011).  Many more essential residues have more recently been identified (Karena et al. 2015). An "ancestral" homolog (AncXanQ) has been constructed and proved to have broader specificity, transporting with high-affinity both xanthine and guanine, but also recognizing adenine, hypoxanthine, and a range of analogs (Tatsaki et al. 2021). AncXanQ conserves all binding-site residues of XanQ and differs substantially in only five intramembrane residues outside the binding site. Tatsaki et al. 2021 subjected both homologs to rationally designed mutagenesis and presented evidence that these five residues are linked with the specificity changes.