Natural Protein Engineering

Thomas, P.G., Russel, A.J., Fersht, A. Tailoring the pH dependence of enzyme catalysis using protein engineering. Nature 318 375-376, 1985. 

Fersht, A.R., et al. Hydrogen bonding and biological specificity analyzed by protein engineering. Nature 314 235-238, 1985. 

Matouschek, A., Kellis,J. T., Serrano, L., and Fersht, A. R. (1989). Mapping the transition-state and pathway of protein folding by protein engineering. Nature 340, 122-126. 

Transient folding intermediates characterized by protein engineering. Nature, 346, 440-445. 

Gibbs CS, Coutre SE, Tsiang M, Li WX, Jain AK, Dunn KE, Law VS, Tao CT, Matsumura SY, Mejza SJ, Paborsky LR, Leung LLK. Conversion of thrombin into an anticoagulant by protein engineering. Nature 1995 378 413-416. 

Coiled-coil motifs have been known to play roles in conformational switching in natural proteins for some time (Oas and Endow, 1994). The key examples are influenza hemagglutinin (Bullough et al., 1994 Carr and Kim, 1993 Carr et al., 1997), and the heat shock transcription factor (Rabindran et al., 1993). Furthermore, an engineered form of GCN4-pl, with Asn-16 replaced by Ala, switches from dimer to trimer upon addition of... 

So far, peptide synthesis has mainly involved the preparation of biologically or pharmaceutically relevant substances, total chemical synthesis of natural proteins or protein engineering. The objective of this chapter is to show how the different methods that have been developed for peptide synthesis can be used to prepare biologically-inspired supramolecular architectures and polymeric materials, which might be of potential interest for a variety of advanced applications. 

In Nature, there are many examples of protein and peptide molecular self-assembly. Of the genetically engineered fibrous proteins, collagen, spider silks, and elastin have received attention due to their mechanical and biological properties which can be used for biomaterials and tissue engineering. 

As scientists and engineers, natural self-assembly processes represent a tremendous resource, which we can use to create our own miniature materials and devices. Our endeavors are informed by hundreds of years of curiosity-driven research interested in the natural world. Our toolbox is further expanded by modem synthetic chemistry which extends beyond the realm of natural molecules. We can also create artificial environments to control and direct assembly and use computer-based tools and simulations to model and predict self-assembly pathways and their resulting protein structures. Many researchers believe we can use these modern tools to simplify, improve, and refine assembly processes. We have much to do in order to reach this ambitious goal but the next 10 years are likely to be filled with exciting discoveries and advances as self-assembling polypeptide materials move from the laboratory to the clinic or the manufacturing assembly line. 

Fersht AR, Shi J-P, Knill-Jones J, Lowe DM, Wilkinson AJ, Blow DM, Brick P, Carter P, Wayne MMY, Winter G (1985) Hydrogen bonding and biological specificity analysed by protein engineering. Nature (Lond) 314 235-238... 

---