6foc

Publication Abstract from PubMed

The crystal structure of the F1-catalytic domain of the adenosine triphosphate (ATP) synthase has been determined from Mycobacterium smegmatis which hydrolyzes ATP very poorly. The structure of the alpha3beta3-component of the catalytic domain is similar to those in active F1-ATPases in Escherichia coli and Geobacillus stearothermophilus However, its epsilon-subunit differs from those in these two active bacterial F1-ATPases as an ATP molecule is not bound to the two alpha-helices forming its C-terminal domain, probably because they are shorter than those in active enzymes and they lack an amino acid that contributes to the ATP binding site in active enzymes. In E. coli and G. stearothermophilus, the alpha-helices adopt an "up" state where the alpha-helices enter the alpha3beta3-domain and prevent the rotor from turning. The mycobacterial F1-ATPase is most similar to the F1-ATPase from Caldalkalibacillus thermarum, which also hydrolyzes ATP poorly. The betaE-subunits in both enzymes are in the usual "open" conformation but appear to be occupied uniquely by the combination of an adenosine 5'-diphosphate molecule with no magnesium ion plus phosphate. This occupation is consistent with the finding that their rotors have been arrested at the same point in their rotary catalytic cycles. These bound hydrolytic products are probably the basis of the inhibition of ATP hydrolysis. It can be envisaged that specific as yet unidentified small molecules might bind to the F1 domain in Mycobacterium tuberculosis, prevent ATP synthesis, and inhibit the growth of the pathogen.

The structure of the catalytic domain of the ATP synthase from Mycobacterium smegmatis is a target for developing antitubercular drugs.,Zhang AT, Montgomery MG, Leslie AGW, Cook GM, Walker JE Proc Natl Acad Sci U S A. 2019 Mar 5;116(10):4206-4211. doi:, 10.1073/pnas.1817615116. Epub 2019 Jan 25. PMID:30683723^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.