Journal:JMB:2

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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

Figure   2.   Structural   details   of   the   2HQ/rePON1   complex   at   pH   6.5;   2HQ   and   the  

structured  active-­site  loop  in  the  rePON1-­2HQ  complex  structure.    Overlay  of  the  phosphate  ion  in  the  apo  rePON1  at  pH  6.5  and  of  2HQ   in  the  rePON1-­2HQ  complex.   The  first  segment  of  the  active-­site  loop,  and  residues  Y71   and  I74  in  particular,  comprises  part  of  PON1's  active-­site  wall.   Interactions  of  2HQ  with   active-­site  residues  (interactions  with  the  catalytic  Ca2+  are  highlighted  in  red).  

.  Changes  in  the  rePON1  binding  site  upon  binding  of  2HQ.  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.  

1. ↑ Ben-David M, Elias M, Filippi JJ, Dunach E, Silman I, Sussman JL, Tawfik DS. Catalytic Versatility and Backups in Enzyme Active Sites: The Case of Serum Paraoxonase 1. J Mol Biol. 2012 Mar 1. PMID:22387469 doi:10.1016/j.jmb.2012.02.042