This was one of the reasons I chose bio over organic chemistry: the distant promise of designing custom proteins from scratch. OK, I went astray and ended up in cell biology and genetics, but hey… it’s the thought that counts :-)!
Design and engineering of an O(2) transport protein, Nature, Mar 2009
Again, the full abstract is below the fold and here is my summary:
It is AMAZINGLY COOL! OMG!!!111oneoneone
… well OK I’ll say a bit more. In a few steps, the authors basically create a protein (from near-scratch) that does what another protein, but found in nature, does: binding and releasing molecular oxygen (O2).
What is fascinating is that, actually, despite doing the same thing, this truly ‘Intelligently Designed’ protein is simpler than its natural equivalent. Plus it has one great advantage: it binds oxygen (O2) better than it binds carbon monoxide (CO). Of course, this is the other way around in “our” oxygen binding proteins, and the cause of many deaths each year.
A nice (I think) “stab” that the authors make (this is in the full article) is towards the reverence that exists towards the natural equivalent of this protein – it has a rather baroque (I suppose is the word) “haemoglobin fold” that is often taken as an example of how nicely complex the “perfect” solutions are that nature has come up with to solve specific complex problems – such as binding oxygen specifically.
Except that this designed protein does not have such a fold, to no detrimental effect. The authors dryly state that that structure in the natural protein may simply still exist not because it is “perfect” but merely because it is “good enough”. Something I think is true of most things in nature on several levels, from genes and proteins to limbs and colour patterns.
It is barely necessary to further refute claims about Intelligent Design (the new word for creationism) but the results of this paper do a very fine job at this, too. It shows that truly “intelligent” design does the same job nature did, but quicker, more to-the-point and with less complexity. Ergo, if “God” really did design these proteins, he did a far crappier job than a bunch of 21st-century scientists. Not a good sign for an omnipotent, omniscient being.
Anyway, let’s not waste too much words on that. The bottom line is that this is great news for fields like biotechnology, where custom-designed proteins may start to do things a whole lot better than current “designs” based on natural proteins (but with modifications, such as the enzymes in washing powder). And, we’re another step closer to creating a truly artificial life form! (Or maybe that is my grandiose megalomaniac delusional mind speaking… whatever.)
Nature. 2009 Mar 19;458(7236):305-9.
Design and engineering of an O(2) transport protein.
Koder RL, Anderson JL, Solomon LA, Reddy KS, Moser CC, Dutton PL.
The Johnson Research Foundation, Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
The principles of natural protein engineering are obscured by overlapping functions and complexity accumulated through natural selection and evolution. Completely artificial proteins offer a clean slate on which to define and test these protein engineering principles, while recreating and extending natural functions. Here we introduce this method with the design of an oxygen transport protein, akin to human neuroglobin. Beginning with a simple and unnatural helix-forming sequence with just three different amino acids, we assembled a four-helix bundle, positioned histidines to bis-histidine ligate haems, and exploited helical rotation and glutamate burial on haem binding to introduce distal histidine strain and facilitate O(2) binding. For stable oxygen binding without haem oxidation, water is excluded by simple packing of the protein interior and loops that reduce helical-interface mobility. O(2) affinities and exchange timescales match natural globins with distal histidines, with the remarkable exception that O(2) binds tighter than CO.