Mechanistic insights into metal (Pd2+, Co2+, and Zn2+)-β-cyclodextrin catalyzed peptide hydrolysis: a QM/MM approach.
In this study, mechanistic insights into the hydrolysis of an extremely stable tertiary peptide bond (Ser-Pro) in the Ser-Pro-Phe sequence by an artificial enzyme, metal (Pd(2+), Co(2+), or Zn(2+))-β-cyclodextrin (CD) complex, have been provided. In particular, the exact reaction mechanism, the location of CD (number of -CH2 groups downstream from the metal center), conformation of CD (primary or secondary rim of CD facing the substrate), the number of CD (one or two), and the optimum metal ion (Pd(2+), Co(2+), or Zn(2+)) have been suggested using a state-of-the-art hybrid quantum mechanics/molecular mechanics (QM/MM: B3LYP/Amber) approach. The QM/MM calculations suggest that the internal delivery mechanism is the most energetically feasible for the peptide hydrolysis. The inclusion of a CD ring at two CH2 groups downstream from the metal center can provide 3 × 10(5) times acceleration in the activity, while the replacement of Pd(2+) with Co(2+) enhances the rate activity another 3.7 × 10(4) times.
Department of Chemistry, University of Miami , 1301 Memorial Drive, Coral Gables, Florida 33146, United States.
Tingting
T
Zhang
Xiaoxia
X
Zhu
Rajeev
R
Prabhakar
D002384:Catalysis; D006868:Hydrolysis; D019216:Metals, Heavy / Q000737:chemistry*; D009942:Organometallic Compounds / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D011789:Quantum Theory; D047392:beta-Cyclodextrins / Q000737:chemistry*
D019216:Metals, Heavy; D009942:Organometallic Compounds; D010455:Peptides; D047392:beta-Cyclodextrins; C031215:betadex