Rational design, protein engineering

Schomburg D (1994) Rational protein design of proteins with new properties. In Wrede P, Schneider G (eds) Concepts in protein engineering and design. De Gruyter, Berlin, p 169... 

Luft S. Beyond directed evolution-semi-rational protein engineering and design. Curr Opin Biotechnol... 

Marshall, S.A., Lazar G.A., Chirino A.J., and Desjarlais J.R. 2003. Rational design and engineering of therapeutic proteins. Drug Discovery Today 8, 212-221. 

Genetic engineering. The X-ray structures are known for many hydrolases, allowing for modeling of the substrate in the active site as well as structurally based, random or rational protein mutation to magnify or invert enantioselectivity. An example of the latter is provided by the rational design of a mutant of Candida antarctica lipase (CALB), which, instead of the wild-type R-selectivity, displayed... 

Aehle, W., Sobek, H., Amory, A., Vetter, R., Wilke, D. Schomburg,D. (1993). Rational protein engineering and industrial application structure prediction by homology and rational design of protein-variants with improved washing performance the alkaline protease from Bacillus alcalophilus. Journal of Biotechnology, 28, 31-40. 

NMR299 300 and other spectroscopic techniques (Fig. 16-18),260 by theoretical computations,301-304 and by protein engineering and "rational design."305 306... 

Despite sharing only 25% sequence identity, structural analysis indicates that both proteins of E. coli NADP-IDH and T. thermophilus NAD-IMDH are homodimers which share a common protein fold that lacks the p p p motif characteristic of the nucleotide binding Rossmann fold [23], The strict and distinct specificities of these enzymes provide an attractive model system for engineering specificity, while the extensive knowledge of substrate and coenzyme binding and catalysis provide the sound foundation critical for rational design. 

In this study we combined two strategies common in protein engineering. Substitutions based on rational design within the nucleotide-binding pocket were used to convert E. coli IDH coenzyme specificity from NADP to NAD, while substitutions improving overall performance were identified by partial random mutagenesis at sites outside the nucleotide-binding pocket [5,12],... 

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