"Designer" protein for oxygen transfer
Anna Sablina, EternalMind.ru
A group of biochemists from the University of Pennsylvania (University of Pennsylvania School of Medicine) has designed a completely new type of protein compared to those found in nature. Its function is the transport of oxygen, as in human globins. It is assumed that such proteins can be used to create artificial blood.
The structure of the protein is simple and its size is small compared to natural proteins. The researchers emphasize that natural proteins are complex and fragile, and the one created by them is simple and reliable. This protein is not a converted natural protein, but a completely new combination of amino acids. The researchers used the most common elements of the structure of natural proteins, such as alpha helices and disulfide bridges, to create a fundamentally new protein, the amino acid sequence of which was completely invented by scientists.
First, an artificial alpha helix sequence was developed, six amino acids per turn, all turns are the same. For this purpose, three types of amino acids were used, arranged according to the AABBCC principle. Two of the amino acids used were hydrophilic (prefer to come into contact with water), one was hydrophobic (prefers to come into contact with hydrophobic molecules), which made it possible to assemble four spirals into a bundle. The presence of a hydrophobic core in this protein is also important because heme and oxygen decompose in water. Amino acids in certain places were replaced with histidine to position heme (an iron-containing heterocyclic organic group necessary for binding oxygen molecules) and glutamate to create tension, thanks to which alpha helices unfold to capture oxygen. The ends of the spirals were connected by disulfide bridges or by means of a loop, the amino acid sequence of which was also developed by scientists, carrying a cysteine residue in the middle to form a disulfide bridge (see Fig.).
Initially, when figuring out the desired amino acid sequence, the researchers used a "synthesizer" – a robot that chemically combines amino acids – to create the first artificial alpha helices. When the desired sequence was found, the Escherichia coli bacterium was used to develop the protein.
When oxygen was bound to heme in the protein composition, the solution changed color from dark red to scarlet, almost the same as that of neurooglobin. The oxygen binding characteristics of artificial protein are similar to those of natural globins with distal histidines, except that molecular oxygen (O2) binds more strongly than carbon monoxide (CO). The latter irreversibly binds to natural hemoglobin, which is the cause of poisoning with this gas during incomplete combustion of organic fuel. This property of the new protein can be very useful when creating artificial blood.
Sources:
Ronald L. Koder et al., Design and engineering of an O2 transport protein //Nature, Vol 458 | 19 March 2009
Karen Kreeger, Proteins by design: Penn biochemists create new protein from scratch // EurekAlert, 23-Mar-2009
Portal "Eternal youth" www.vechnayamolodost.ru30.03.2009