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Research Abstracts Online
January 2010 - March 2011

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University of Minnesota Twin Cities
College of Science and Engineering
Department of Chemistry

PI: Mark D. Distefano

Modeling the Transition State of Farnesylation Reaction With Unnatural Substrate

The Protein Farnesyl Transferase (PFTase) is an enzyme involved in post-translational modification of RAS proteins. The inhibition of PFTase prevents tumor cells growth, thus, PFTase inhibitors can be efficient anti-cancer drugs. Since the enzyme binds TS much tighter than substrate TS analogs can be the most potent inhibitors. TS analogs can be designed if the structure of the TS in enzymatic reaction is known. The model of the TS structure was built using Gaussian program. Unnatural substrates might react via distorted TS. Analysis of the reactivity of the unnatural substrates allows for analysis of the flexibility of the enzyme. This knowledge will allow researchers to refine the structures of the PFTase inhibitors of interest. The results would show the key features of the PFTase catalysis and provide guidelines for TS analogues design.

Group Members

Daniel Abate Pella, Graduate Student
Jonathan Dozier, Graduate Student
Olivier Henry, Research Associate
Stepan Lenevich, Graduate Student
Dan Mullen, Research Associate
Mohammad Rashidian, Graduate Student