6FOC

F1-ATPase from Mycobacterium smegmatis

Summary for 6FOC

• Entry DOI: 10.2210/pdb6foc/pdb
• Descriptor: ATP synthase subunit alpha,ATP synthase subunit alpha,ATP synthase subunit alpha, ATP synthase subunit beta, ATP synthase gamma chain, ... (8 entities in total)
• Functional Keywords: complex, mycobacteria, hydrolase
• Biological source: Mycolicibacterium smegmatis MC2 155; More
• Total number of polymer chains: 8
• Total formula weight: 380693.17

Authors

Zhang, T.,Montgomery, M.G.,Leslie, A.G.W.,Cook, G.M.,Walker, J.E. (deposition date: 2018-02-06, release date: 2019-01-23, Last modification date: 2024-01-17)

Primary citation

Zhang, A.T.,Montgomery, M.G.,Leslie, A.G.W.,Cook, G.M.,Walker, J.E.
The structure of the catalytic domain of the ATP synthase fromMycobacterium smegmatisis a target for developing antitubercular drugs.
Proc.Natl.Acad.Sci.USA, 116:4206-4211, 2019

PubMed Abstract: The crystal structure of the F-catalytic domain of the adenosine triphosphate (ATP) synthase has been determined from which hydrolyzes ATP very poorly. The structure of the αβ-component of the catalytic domain is similar to those in active F-ATPases in and However, its ε-subunit differs from those in these two active bacterial F-ATPases as an ATP molecule is not bound to the two α-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 and , the α-helices adopt an "up" state where the α-helices enter the αβ-domain and prevent the rotor from turning. The mycobacterial F-ATPase is most similar to the F-ATPase from , which also hydrolyzes ATP poorly. The β-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 F domain in , prevent ATP synthesis, and inhibit the growth of the pathogen.

PubMed: 30683723
DOI: 10.1073/pnas.1817615116

Experimental method

X-RAY DIFFRACTION (4 Å)