4/19/2023 0 Comments Protein scaffold engineeringHowever, the fact that there are a considerable number of glycan-related genes in our genome (e.g. The molecular mechanisms of these biological phenomena involving glycans and their functions are not fully understood. In fact, all biological organisms spend much effort not only on the synthesis of glycans but also on their recognition or ‘decoding’ by a variety of carbohydrate-binding proteins or lectins (historically called haemagglutinin or agglutinin), and on their degradation by a series of endo- and exo-glycosidases. Among these modifications, glycosylation is the most dominant and even complex. Although the central dogma defines a direction of genetic information flow from DNA to protein via an intermediate molecule, RNA, most of the resultant proteins do not remain ‘naked’ but are subject to extensive post-translational modifications. Soon after the word proteome appeared in 1995, the word glycome was coined by a few glycoscientists simultaneously at the end of the twentieth century. DNA, protein and glycan, in a biological species is called its genome, proteome and glycome, respectively. The total set of these biomolecules, i.e. sialylation, fucosylation, sulfation, etc.) are largely identical. In the case of glycoproteins, there are also further structural types, largely divided into N-glycans and O-glycans, which are biosynthesized using different construction principles by different sets of glycosyltransferases, although their non-reducing terminal modifications (e.g. Glycans usually exist as glycoconjugates, glycoproteins, proteoglycans and glycolipids, rather than existing in a free state. Even if this can be achieved, there is an additional complication. Thus, unlike DNA and peptides, it is difficult to develop a systematic principle to facilitate automated sequencing and synthesis for glycans. nucleotides and amino acids, respectively) are connected by a single linkage pattern, the former (glycans) are often branched with multiple linkage isomers. Although the latter two are ‘linear’ molecules, in which component molecules (i.e. Glycans are regarded as the third group of biopolymers for which rich structural diversity and biological information is available, following nucleic acids (DNA and RNA) and proteins (polypeptides). However, for this discussion, it is worth first mentioning their counterpart or receptor molecules, glycans. How to ‘create’ lectins from an engineering viewpoint is a theme of this review. Likewise, the protein structures that we design and produce in vitro will have limitations, probably because we are likely to use existing protein scaffolds as starting materials and templates when we perform mutagenesis and engineering experiments. In this review, possible approaches to confer sugar-binding properties on synthetic proteins and peptides are described.įrancois Jacob described in The possible and the actual how our imaginations cannot completely overcome our past experiences as evidenced by the depictions of aliens in scientific fiction and chimeric creatures in Greek mythology. However, the above observation implies that any protein scaffold, including those that have never been described as lectins, may be modified to acquire a sugar-binding function. Based on the current state of the art, various methods of lectin engineering are available, by which lectin specificity and/or stability of a known lectin scaffold can be improved. It is also expected that new lectin domains including those found in enzymes as carbohydrate-binding modules will be generated in the future through evolution, although this has never been attempted on an experimental level. This fact suggests that new lectins will be discovered either by a conventional screening approach or just by chance. According to a recent report, there are more than 50 lectin scaffolds (∼Pfam), for which three-dimensional structures are known and sugar-binding functions have been confirmed in the literature, which far exceeds our view in the twentieth century (Fujimoto et al. Lectins are a widespread group of sugar-binding proteins occurring in all types of organisms including animals, plants, bacteria, fungi and even viruses.
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