Document Detail

Pressure effects on enzyme-catalyzed quantum tunneling events arise from protein-specific structural and dynamic changes.
MedLine Citation:
PMID:  22632111     Owner:  NLM     Status:  Publisher    
The rate and kinetic isotope effect (KIE) on proton transfer during the aromatic amine dehydrogenase-catalyzed reaction with phenylethylamine shows complex pressure and temperature dependences. We are able to rationalize these effects within an environmentally-coupled tunneling model based on constant pressure molecular dynamics simulations. As pressure appears to act anisotropically on the enzyme, perturbation of the reaction coordinate (donor-acceptor compression) is, in this case, marginal. Therefore, while we have previously demonstrated that pressure and temperature-dependences can be used to infer H-tunneling and the involvement of promoting vibrations, these effects should not be used in the absence of atomistic insight as they can vary greatly for different enzymes. More generally, we We show that a pressure-dependent KIE is not a definitive hallmark of quantum mechanical H-tunneling during an enzyme-catalyzed reaction and that pressure independent KIEs cannot be used to exclude tunneling contributions or a role for promoting vibrations in the enzyme-catalyzed reaction. We conclude that coupling of molecular dynamics calculations with experimental rate and KIE studies is required to provide atomistic understanding of pressure effects in enzyme catalyzed reactions.
Sam Hay; Linus O Johannissen; Parvinder Hothi; Michael John Sutcliffe; Nigel Shaun Scrutton
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-5-26
Journal Detail:
Title:  Journal of the American Chemical Society     Volume:  -     ISSN:  1520-5126     ISO Abbreviation:  -     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-5-28     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7503056     Medline TA:  J Am Chem Soc     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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