Biochemical controls: reading DNA (Introduction)

by David Turell @, Saturday, September 10, 2022, 16:16 (536 days ago) @ David Turell

At enormous speeds:

"This team worked on a helicase enzyme named PcrA, which unwinds DNA for transcription. This enzyme works so fast (1000 bases per second!) it’s been like trying to describe the blur of a racecar speeding down a track. Using a new technique called “single-molecule picometer-resolution nanopore tweezers” (SPRNT), they were able to slow down the action and watch the racecar move with its “inchworm mechanism” one base at a time. This blends chemistry with another branch of physics, mechanics: “mechanochemistry.” (my bold)

"We recorded more than two million enzyme steps under various assisting and opposing forces in diverse adenosine tri- and diphosphate conditions to comprehensively explore the mechanochemistry of PcrA motion.…Our data reveal that the underlying DNA sequence passing through the helicase strongly influences the kinetics during translocation and unwinding. Surprisingly, unwinding kinetics are not solely dominated by the base pairs being unwound. Instead, the sequence of the single-stranded DNA on which the PcrA walks determines much of the kinetics of unwinding.

"The authors are not clear why this is. What is evolution up to? They figure that there must be a reason.

"Unlike protein filaments (e.g., actin), DNA is not a homogeneous track; sequence-dependent behavior may be the norm rather than the exception. Strong sequence-dependent enzyme kinetics such as those observed in our data likely affect PcrA’s role in vivo and could thereby exert selective pressure on both DNA and protein evolution. Therefore, sequence-dependent behavior should be carefully considered in future studies of any enzyme that walks along DNA or RNA, since the sequence-dependent kinetics may reveal essential features of an enzyme’s function. Such effects are almost certainly used by life to achieve various ends, and SPRNT is well suited to discovering how and why such sequence dependence occurs and opens the possibility of uncovering enzyme functions that were hereto unknown.

"Why are they giving the credit to blind evolution? If life uses “sequence-dependent kinetics…to achieve various ends,” that sounds like intelligent design, not evolution. Design advocates are accustomed to forgiving logical malapropisms like this. They look past the magical thinking and see the operation of a designing mind with foresight and purpose, intimately familiar with the laws of physics, able to write code to utilize those laws in precision operations. Now, it becomes clear that the precision goes deeper than previously known."

Comment: The final paragraph is pure ID thought. The unwinding speed of PcrA is amazing. What should be mentioned is all enzymes are giant molecules of thousands of amino acids. How did natural evolution find it?

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