ATP synthase, the rotary engine in all living things, has another trick in its design specs: a ratcheting mechanism that improves the efficiency of ATP synthesis. ATP is the “energy currency” of cellular life, so the efficiency of production of ATP is of vital importance.
Three European scientists, reporting in PNAS, used quantum mechanical approaches to study the energy flow during production of ATP in the beta subunits (the active sites of the motor-driven enzyme). The alpha subunit rotates like a waterwheel, engaging a camshaft called the gamma subunit. Three ATP are formed in the beta portion for each 360° cycle. That results in one ATP for each 120 degrees of rotation: “There are three active sites at which the reaction may take place and these are subject to conformational changes during the revolving cycle,” they explained (a conformational change indicates moving parts). Hints that more was going on each 1/3 turn were brought to light when other researchers noticed slight pauses at 90° and 30°.
The authors found two transition states within the 120° motion that favor the reaction one way, like a ratchet. The first of these transition states occurs via a double proton transfer. The second occurs via a conformational change as the third phosphate ion bonds with oxygen on ADP (adenosine diphosphate), forming ATP (adenosine triphosphate). “These two TSs [transition states] are concluded crucial for ATP synthesis,” they said. They found that as the enzyme progresses into these states, energy barriers are set up that block the reverse direction, just like a ratchet on a tool. “This change could indicate a ‘ratchet’ mechanism for the enzyme to ensure efficacy of ATP synthesis by shifting residue conformation and thus locking access to the crucial TSs.”
It’s “demanding” to study these machines. “The complex function of ATP synthase makes this enzyme special compared to many other enzymes and makes computational investigation challenging,” they said. Many other teams study these amazing molecular machines, and a full understanding of the reaction mechanism awaits elucidation, but the authors felt “we have shown how the positions of alpha-S344 and alpha-R373 [two amino acid residues in the active site] may drastically influence the rate and, in this way, attenuate the reversal of these reaction steps.”
Since ATP synthase is known to permit both synthesis and hydrolysis of ATP, (i.e., the motor is reversible), it will be interesting to see if the ratchets have some kind of clutch mechanism to favor hydrolysis under certain conditions.
Over the last eight years of reports on ATP synthase in these pages, the trend has been to find more and more detail supporting efficient design, and less and less credibility these molecular rotary engines could have evolved by chance. Remember that they are vital to every living cell – even primitive bacteria. Now we see that individual amino acid positions in the active site are critical. Even “point mutations of alpha-S347Q and alpha-S347A have dramatic effects on ATP synthase function both for synthesis and hydrolysis,” they said, pointing out that one known mutation reduces function and another disables it altogether. No wonder these amazing machines are “highly conserved” (unevolved) in all domains of life.
The authors did not mention evolution except for one quick stink bomb, “Performing this reaction efficiently is likely a key biochemical reason for the early evolutionary development of the enzyme complex, so understanding the detailed catalytic steps is most desirable.” What? The need for efficiency somehow caused accidents to occur that “developed,” in some blind, unguided way, this finely-tuned, multi-part, 100% efficient engine beyond human capability to manufacture? “Evolutionary development” is an oxymoron, like blind guide. Let’s repair the sentence: “Performing this reaction efficiently is likely a key biochemical reason for the original design of the enzyme complex, so understanding the detailed catalytic steps is most praiseworthy.” Ah, much better.
 Tamás Beke-Somfai, Per Lincoln, and Bengt Nordén, “Double-lock ratchet mechanism revealing the role of [alpha]SER-344 in F0F1 ATP synthase,” Proceedings of the National Academy of Sciences, published online before print March 7, 2011, doi: 10.1073/pnas.1010453108, http://www.pnas.org/content/early/2011/03/02/1010453108.short.
 The authors measured energy barriers of 43 kJ/mol and 40 kJ/mol in the two transition state ratchets.
Source: Creation-Evolution Headlines, http://creationsafaris.com/crev201103.htm#20110316a