Figure 1: F1-ATP synthase in the inner mitochondrial membrane Institute_of_microbiology

Molecular Mechanics:

How IF1 and Polyphenols inhibit the F1-ATPase

 

New Understandings of the World's Smallest Rotary Motor

The F1-ATPase is the world's smallest known rotary motor. The primary role of the ATPase enzyme is to catalyze the synthesis of ATP, a high energy compound that is used as cellular currency for many metabolic pathways. However, the entire function of the enzyme is not fully understood. In vivo, F1-ATPase has only been observed catalyzing the synthesis of ATP by a rotary mechanism. However, in vitro studies suggest that the enzyme also hydrolyses ATP via a reverse mechanism (Noji et. al.). Past studies have demonstrated that the rotary mechanism of the ATPase can be inhibited when two inhibitory molecules, IF1 and resveratrol bind to specific sites in the enzyme. The inhibitory mechanisms that these inhibitors employ have not been understood because the crystal structure of the enzyme-inhibitor complexes were not solved.

Recently, Gledhill et. al. (August and October 2007) obtained protein crystal structures of F1-ATPase inhibited by IF1 and resveratrol. These structures provide models for further analysis of the complicated inhibitory mechanisms that these inhibitors employ.

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Introduction
Background
Discovery
Medical Implications
References
 
  Author: Natalie Marie Pace/ Biochemistry 462b Honors Project / The University of Arizona / Last revised May14 2008