FRCD

General Function:

Transporter activity

Specific Function:

Mitochondrial membrane ATP synthase (F(1)F(0) ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain. F-type ATPases consist of two structural domains, F(1) - containing the extramembraneous catalytic core, and F(0) - containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation. Subunits alpha and beta form the catalytic core in F(1). Rotation of the central stalk against the surrounding alpha(3)beta(3) subunits leads to hydrolysis of ATP in three separate catalytic sites on the beta subunits.

Gene Name:

ATP5B

Uniprot ID:

P06576

Molecular Weight:

56559.42 Da

Mechanism of Action:

Aurovertins are a mixed, noncompetitive inhibitors of both ATP hydrolysis and synthesis. They do this by inhibiting the proton-pumping F1F0-ATP synthase by binding to beta-subunits in its F1 catalytic sector. F1F0-ATP synthase is responsible for the terminal step of oxidative phosphorylation. Each ATP synthase complex has three beta subunits, and aurovertins are believed to bind with varying affinity to two subunits on sites in a cleft between the nucleotide-binding and C-terminal domains, thus preventing closure of the catalytic interfaces necessary for the cyclic interconversion of catalytic sites.

References

1. Johnson KM, Swenson L, Opipari AW Jr, Reuter R, Zarrabi N, Fierke CA, Borsch M, Glick GD: Mechanistic basis for differential inhibition of the F1Fo-ATPase by aurovertin. Biopolymers. 2009 Oct;91(10):830-40. doi: 10.1002/bip.21262. [19462418 ]