Design of functional metalloproteins

_{Mario Lopez

August 12, 2009

Intelligent Design, Science}

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NATURE|Vol 460|13 August 2009|doi:10.1038/nature08304 REVIEW

Yi Lu1, Natasha Yeung1, Nathan Sieracki1 & Nicholas M. Marshall1

Metalloproteins account for nearly half of all proteins in nature. Protein
metal-binding sites are responsible for catalysing important biological
processes, such as photosynthesis, respiration, water oxidation, molecular
oxygen reduction and nitrogen fixation. Much effort has been devoted
to understanding the structure and function of metalloproteins, as summarized
by other reviews in this Insight. The ultimate test is to use this
knowledge to design new metalloproteins that reproduce the structures
and functions of native metalloproteins1–3. Metalloprotein design is not
just an intellectual exercise that duplicates biochemical and biophysical
studies of native metalloproteins. This ‘bottom-up’ approach can also elucidate
structural features that may remain hidden in those studies. Whereas
biochemical and biophysical studies mostly reveal individual features that
result in a loss of function, design requires the incorporation of all the
structural features needed to attain a function. Equipped with insights
from design processes, it may be possible to design new metalloproteins
with improved properties such as higher stability and greater efficiency,
or to impart them with functions not found in nature, for use in an even
wider range of biotechnological and pharmaceutical applications.

Comments

Thank you, Nakashima. Actually, it is clear if it demonstrates that "design" principles are necessary to attain a functional sequence. Unlike your example, no function is evident nor necessary. To improve on a functional sequence does not disprove design altogether, albeit I would concede the possibility of defective/imperfect design. However, I am convinced that entropy is a better candidate to explain the degradation of an aboriginal design. In this case, of course, it is the effects of random mutations that degrade the function of metalloproteins, not entropy. Entropy is postponed, so to speak, in living systems as a result of the use of natural energy resources. :)Mario A. Lopez_{August 14, 2009
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Mr Lopez, Obviously, designers can improve on presently existing designs (especially those that are affected by entropy), but clearly design is already present. That last phrase is always the problem. No, design is not 'clearly' present. It isn't clear by its perfection, since it is being improved upon (and you are quite aware of this with your appeal to entropy). Its not categorically different from what you would expect in a material explanation, after all the ocean is full of dissolved metals. To appeal to design here, you will have to calculate some aspect of FSCI above and beyond what the laws of chemistry and evolution can produce.Nakashima_{August 14, 2009
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"What exactly is “directed evolution”?" Indeed.IRQ Conflict_{August 13, 2009
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PB, Here is another gem: "Although approaches based on empirical knowledge and rational design using computer programs have been relatively successful in designing metalloproteins, it is still difficult to design certain metalloproteins, especially functional ones, owing to the large number of potential interactions within the active site of a metalloenzyme. In this case, combinatorial design and directed evolution of new metalloenzymes is another powerful method. For example, directed evolution has been extensively applied to antibodies to develop new metalloenzymes." What exactly is "directed evolution"? Induced mutations in specific sites? Combinatorial manipulation? Is this not "design" as in "intelligent" design?Mario A. Lopez_{August 13, 2009
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PaulB, I found this rather interesting for several reasons. I often say that it is difficult to remove "design" language from the science literature because of the informational and functional aspects found within nature. This is such an example: "Equipped with insights from design processes, it may be possible to design new metalloproteins with improved properties such as higher stability and greater efficiency, or to impart them with functions not found in nature..." Perhaps greater efficiency is attainable, but what are they trying to make more efficient by utilizing design principles? Obviously, designers can improve on presently existing designs (especially those that are affected by entropy), but clearly design is already present. Design principles are necessary to elucidate hidden functional properties precisely because "biochemical and biophysical studies mostly reveal individual features that result in a loss of function". I am not saying that the authors are design proponents (I am not sure that they are even aware that they might be), but that "design" makes for a good heuristic to spur scientific discovery. :)Mario A. Lopez_{August 13, 2009
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Okay, I'll bite: Why is this article important? Are Lu, Yeung, Sieracki or Marshall intelligent design proponents? Or is it just that the word "design" (having nothing whatsoever to do with intelligent design) appears in the article? I'm puzzled.PaulBurnett_{August 12, 2009
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