Enzyme created in test tube displays new structure, function

January 17, 2013 by Lori Ann White
This image shows changes in the 3-D structure of the original protein scaffold (left) upon directed evolution of the scaffold to the artificial RNA ligase enzyme (right). Click image for full diagram. Credit: Seelig, et al.

(Phys.org)—Five years ago, a pair of researchers used a clever update on a technique called in vitro evolution – evolution in a test tube – to turn an ordinary protein into an artificial enzyme, a biological catalyst capable of joining two segments of RNA. It was the first time this had ever been done.

Now, a study partially conducted at SLAC's Stanford Synchrotron Radiation has revealed the true extent of their success: not only was the the first one known to carry out this particular reaction, but it had taken on a new, essentially "primordial" structure never seen in proteins before.

On a practical level, said Seelig, this technique of in vitro directed evolution has the potential to produce new enzymes for a range of applications, such as drug development or biofuel production, without being limited to the familiar ways proteins fold themselves into compact structures.

In the original 2007 paper, published in Nature, Jack W. Szostak of the Howard Hughes Medical Institute and Massachusetts General Hospital and Burckhard Seelig, now at the University of Minnesota, explained their process. They started with a protein that showed no , made many copies of it that contained random structural mutations, tested the copies to see if any of the had enzyme-like properties, and selected the most promising candidates to copy and mutate again. Several rounds of this in vitro evolution resulted in the artificial enzyme, called a ligase enzyme. Ligase enzymes forge bonds between molecules and many different types exist, but the artificial enzyme the team created does not seem to have a counterpart in nature.

Though they knew what went into their new enzyme and they knew it worked, the two scientists didn't yet know why or how. During subsequent investigations into the nature of the artificial enzyme, Seelig and his team of researchers brought samples of it to SSRL. There, Staff Scientist Ritimukta Sarangi used a powerful X-ray spectroscopy technique that, along with nuclear magnetic resonance (NMR) imaging, gave them a good look at the enzyme's unique structure. What they found, as documented recently in Nature Chemical Biology, was a structure with little resemblance to the original protein – in fact, it had little resemblance to existing enzymes either.

Proteins are made up of long chains of amino acids, and the way these chains fold into a compact structure is vital to the protein's function. Entire families of enzymes with similar folds have been identified and studied, and one of the most important aspects of studying a new protein is determining how it folds. The researchers found that the artificial enzyme kept a zinc "spine" from the original protein, but discarded that protein's way of folding and developed its own. What's more, the artificial enzyme was much more flexible than the parent protein, with a simpler structure than usual for an enzyme.

According to Seelig, the simplified environment of in vitro evolution might be the source of such a primitive , and since the has not been subjected to the billions of years of natural evolution that shaped contemporary enzymes, the way it folds can be viewed as an early or "primordial" fold.

Explore further: Discovery of new protein could provide new understanding of male fertility

More information: www.nature.com/nchembio/journal/vaop/ncurrent/full/nchembio.1138.html

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2.3 / 5 (3) Jan 17, 2013
When will these filthy scientists finally realize that evolution is impossible according to the laws of thermodynamics.

2.3 / 5 (3) Jan 17, 2013
@VendicarD I know you are somewhat biased towards the real position of evolution in a multitude of forms, yet you appear to provoke the creationists and others of similar simplistic lower intellectual capacity and status to sprout forth their vitriol and deadpan responses derived from a purely static religious work of nonetheless than the aggrandised Moses, surely that period has elapsed with the benefit of your kind attention of the preceding 12 months or so.

The converts to evolution are now mostly silent and those diametrically opposed have either lost interest or are so tired they use their old testament now as a door stop (after having read it one last time - of course)...

Can we move on to more enlightened speculative discussion which will, for sure, leave the adherents to static approaches as found in obtuse religious far in the dust from our exhaust trails ?

1 / 5 (1) Jan 17, 2013
@VendicarD I keep seeing statements like this from the lot of you, yet what I've yet to see is anything describing how evolution is and the laws of thermodynamics aren't compatible. You call us idiots, yet you make dumb statements and refuse to actually support them with citations and supporting material.

@mike ID is ridiculous, even to those of us who are religious and not silly in our ignorance of the sciences.

Cardinal Paul Poupard -- "the faithful have the obligation to listen to that which secular modern science has to offer, just as we ask that knowledge of the faith be taken in consideration as an expert voice in humanity. We also know the dangers of a religion that severs its links with reason and becomes prey to fundamentalism."

not rated yet Jan 18, 2013
I think Vendicar made a joke?^^ I mean to post such a comment unde a direct observation of evolution in the testtube is really ridicoulus...it must be a joke, and if so it was a really good one.
not rated yet Jan 18, 2013

If he was joking, I'd feel much more comfortable. Unfortunately he's not. I think evolution took the wrong track with him prior to his birth, leaving him a bit sub-average. Probably explains his animosity towards the sciences.
not rated yet Jan 18, 2013
When will these filthy scientists finally realize that evolution is impossible according to the laws of thermodynamics.

Because we know that evolution is true, the second law of thermodynamics must be false. Assuming of course that the original sentence is true.

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