Biological complexity: ATP molecular machines seen clearly (Introduction)

by David Turell , Friday, March 10, 2023, 20:58 (624 days ago) @ David Turell

The molecules act in more precise and amazing ways than previously imagined:

https://www.sciencedaily.com/releases/2023/03/230309101344.htm

"F-Type ATP synthase, a catalytic complex of proteins, synthesizes adenosine triphosphate (ATP), the energy currency of living cells. A lot of ambiguity exists over the rotational mechanism of this spinning enzyme. Now, researchers from Japan have demonstrated how each chemical event of ATP metabolism is linked to the 'stepwise' rotational movement of the F1 component of ATPase. Especially, they clarified the angle of shaft rotation before ATP-cleavage, a long-standing enigma, to be 200°.

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"Previous investigations of the F1 subunits of Bacillus PS3 have established that ATP cleavage involves chemomechanical coupling, i.e., each rotational stepping motion is linked to a chemical reaction step. The angle of rotation between ATP binding and its cleavage at the same catalytic site has been previously estimated to be 200°. However, experimental evidence to substantiate this has so far been lacking. To address this, the researchers studied the rotation by creating a hybrid F1 using one mutant β and two wild type βs. Since the rate of both ATP cleavage and ATP binding was extremely slow in the mutant, the researchers could observe the pauses or dwells between rotational steps easily.

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"With this study, the authors have resolved a long-term debate over the ATP-cleavage shaft angle and established the chemomechanical correlation of ATPase function. Talking about the future impacts of their novel study, Associate Prof. Masaike elaborates, "Since F1-ATPase is the world's smallest biological rotational motor protein, it can be used as a reference to understand the mechanism of energy transduction in living organisms. This knowledge can be revolutionary in developing efficient nanomachines. Moreover, ATP synthase from Mycobacterium tuberculosis has recently been identified as a potential target for drug discovery. Therefore, to stop its rotation using inhibitors, understanding the mechanism of rotation is quite important."

Comment: this is irreducibly complex and had to be developed intact all at once. Chance is an impossible event.