Survey entry #4

ATP synthase

Author of entry: Achim Schnaufer   |   Organism: Trypanosoma brucei   |   Date submitted: 2007-06-30

Gene links: Tb927.3.1380; Tb927.7.7420.

Description:
The mitochondrial ATP synthase complex is essential in bloodstream form T. brucei (1). In contrast to its counterpart in the mammalian host, the trypanosome enzyme functions in reverse (i.e. ATP hydrolase activity) to pump protons out of the mitochondrial matrix, thus generating the essential mitochondrial membrane potential. Inhibitors specific for the hydrolase direction (i.e. not affecting the synthase direction) would be expected to be potent and specific trypanocides. Such inhibitors are currently under development in the pharmaceutical industry as cardioprotective agents (2), raising the possibility of a piggybacking approach. (1) Schnaufer et al. (2005). EMBO J. 24 (23): 4029-4040. (2) Atwal et al. (2004) J. Med. Chem. 47(5):1081-4 Target ID: geneDB number = multiprotein complex (e.g. Tb927.7.7420, Tb927.3.1380) EC number (if enzyme) = 3.6.3.14 target name = ATP synthase Assay: Assay exists but not yet in microtitre plate format Availability: No useful expression system is available Activity: Significant (= 1 full time person)

Target ID: geneDB number = multiprotein complex (e.g. Tb927.7.7420, Tb927.3.1380) EC number (if enzyme) = 3.6.3

Validation: Genetic OR chemical evidence

Assay status: Assay exists but not yet in microtitre plate format

Availability: No useful expression system is available

Activity: Significant (>= 1 full time person)

References:

Small molecule mitochondrial F1F0 ATPase hydrolase inhibitors as cardioprotective agents. Identification of 4-(N-arylimidazole)-substituted benzopyran derivatives as selective hydrolase inhibitors. (2004). J Med Chem 47: 1081-4. PubMed, Publisher.

The F1-ATP synthase complex in bloodstream stage trypanosomes has an unusual and essential function. (2005). EMBO J 24: 4029-40. PubMed, Publisher.