Hydration waters critically influence catalysis by CPO

PHYS 319

David C. Chatfield, David.Chatfield@fiu.edu, Cassian D'Cunha, cdcun001@fiu.edu, and Carlos Alvarez, alvarez1@stis.net. Department of Chemistry and Biochemistry, Florida International University, University Park, Miami, FL 33199
The mechanism of chlorination of a model beta-diketone substrate by chloroperoxidase (CPO) is studied theoretically. Reaction has been postulated to occur either at the active site or free in aqueous solution. In the latter case, the chlorinating agent is hypochlorous acid created and released by CPO. Both mechanisms are studied, using DFT for solution conditions and QM/MM for enzyme-bound calculations. Reaction barriers and even protonation states of products and reactants are found to be extremely sensitive to the number of explicit waters used in the model, almost all the way to a complete hydration sphere. Thus even for enzyme bound reaction, modeling of explicit waters at the active site is critical, and this is true of possible hydrating waters as well as waters explicitly involved in reaction.

PHYS Poster Session - Water Mediated Interactions
7:30 PM-10:00 PM, Wednesday, August 20, 2008 Pennsylvania Convention Center -- Hall C, Poster

Division of Physical Chemistry

The 236th ACS National Meeting, Philadelphia, PA, August 17-21, 2008