Superimposition of PDE5A1-vardenafil (green and cyan ribbons and green bonds) over PDE5A1-sildenafil (golden ribbons and blue bonds). As a consequence of the different positions of both H-and M-loops between the PDE5A1 complexes of vardenafil and sildenafil, Tyr676, Cys677, and Ile680 interact with vardenafil, whereas Asn662, Ser663, and Leu804 interact with sildenafil. B, superposition of vardenafil (green) over sildenafil reported early by our group (Wang et al., 2006). C, superposition of sildenafils reported by us (Wang et al., 2006) (green), by Zhang et al. (2004) (gold), and by Sung et al., (2003) (cyan). D, superposition of vardenafils from the same three groups.