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Evolution of new binding sites

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Notes on the evolution of new/modified binding sites, eventually for an article.




Directed Evolution
Finally, we note that in recent years, "directed evolution" (or in vitro evolution or molecular evolution) has been used to obtain proteins, often enzymes, with modified properties. In brief, this work involves random mutations in DNA followed by a selection process for the best-fitted. Such work has provided new enzymes with altered substrate specificity, specific activity, topology, enantioselectivity, thermal stability, and resistance to organic solvents. There is an extensive literature. To cite two recent papers (2003) in The Proceedings of the National Academy of Sciences, Williams and coworkers modified the stereochemistry of an aldolase (8) and Leong and co-workers optimized the expression and specific activity of an interleukin, IL-12 (9). We also cite the classic work of Hartley (10), a recent book (11), and a short review (12).
8. Williams, G. J.; Domann, S.; Nelson, A.; Berry, A. Proc. Nat. Acad. Sci. USA 2003, 100, 3143"3148. ["Modifying the stereochemistry of an enzyme-catalyzed reaction by directed evolution." "cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12626743 PubMed "tool=pubmed&pubmedid=12626743 PMC Full text
9. Leong, S. R.; Chang, J. C.; Ong, R.; Dawes, G.; Stemmer, W. P.; Punnonen, J. Proc. Nat. Acad. Sci. USA 2003, 100, 1163"1168. ["Optimized expression and specific activity of IL-12 by directed molecular evolution." "cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12529500 PubMed "tool=pubmed&pubmedid=12529500 PMC Full text
10. Hartley, B. S. Proc. R. Soc. Lond. B 1979, 205, 443"452. ["Evolution of enzyme structure" "cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=42054 PubMed
11. Directed Molecular Evolution of Proteins; Brakmann, S., Johnsson, K., Eds.; Wiley-VCH: Weinheim, Germany, 2002. "ID=104087211&CRETRY=1&SRETRY=0 Table of Contents at Wiley InterScience
12. Alexeeva, M.; Carr, R.; Turner, N. J. Org. Biomol. Chem. 2003, 1, 4133"4137. ["Directed evolution of enzymes: new biocatalysts for asymmetric synthesis." "cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14685314 PubMed "&Yr=2003&VOLNO=%26nbsp%3B%3Cb%3E1%3C%2Fb%3E&Fp=4133&Ep=4137&JournalCode=OB&Iss=23 PDF "FURL=/ej/OB/2003/b311055a.PDF HTML
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