Catalytic versatility and backups in enzyme active sites: The case of serum paraoxanase 1
Moshe Ben-David, Mikael Elias, Jean-Jacques Filippi, Elisabet Dunach, Israel Silman, Joel Sussman and Dan Tawfik, PhD [1]
Molecular Tour
Previously PON1 was . We sought a physiologically active pH and . Note . Especially, observe the . We also solved PON1 at 6.5 pH in . Here, we for the first time observe ordered . The residues colored red . , suggesting that lactone adopt a similar position. 2HQ makes contact with .
(). Superimposition of the rePON1- 2HQ complex (cyan; the closed conformation) with the apo rePON1 structures at pH 4.5 (orange) and pH 6.5 (blue) (the open conformations). The pH 4.5 conformation prevents closure of the active- site loop due to clashes of F347 and H348 with the loop residues (e.g. F77 and I74). Also illustrated is the movement of Y71 (dashed arrow) upon binding of 2HQ, and its interaction with D183 in the 2HQ complex structure.
