Hi Im wondering if you can help me explaining the mechanism

Hi I\'m wondering if you can help me explaining the mechanism using in this article regarding to Kemp elimination using computational catalytic mechanism. I have a hard time understanding its mechanism: how the combinations of Asp or Glu; imidazole of His, how the presence of H bond donor and pi-stacking interaction take place in this mechanism.

link of journal:

http://www.nature.com/nature/journal/v453/n7192/full/nature06879.html

Solution

In this mechanism enzymes are being used which make it catalytic.The key step is the deprotonation i.e. Removal (transfer) of proton of carbon by bases such as carboxylate group of Asp or Glu side chain and imidazole of His which is polarised by carboxylate group of Asp or Glu.When the strength of His in solution i.e. pka becomes too high it becomes double protonated resulting as ineffective base.Then an additional functional group is being added to facilitate catalysis.To stabilize the developed negative charge on oxygen a hydrogen bond donor is used.Catalytic motifs i.e. Acid-base-nucleophile triad lacking H bond donor are also tested because developing negative charge is small in transition state and easily solvated by water.Then aromatic amino acid side chains gets stacked using pi-stacking geometries(the interaction of benzene with non-aromatic compound are higher thus pi-bond localizing is favouring pi stacking interactions).