Natural evolution proteases

Najera I, Richman DD, Olivares I, Rojas JM, Peinado MA, Perucho M, Najera R, Lopez GaHndez C (1994) Natural occurrence of drug resistance mutations in the reverse transcriptase of human immunodeficiency virus type 1 isolates. AIDS Res Hum Retroviruses 10 1479-1488 Nijhuis M, Boucher CAB, Schipper R Leitner T, Schuurman R, Albert J (1998) Stochastic processes strongly influence HIV-1 evolution during suboptimal protease inhibitor therapy. Proc Natl Acad Sci USA 95 14441-14446... 

The PK-resistance of PrPSc is an easily measurable operational parameter that has played a fundamentally important role in the evolution of concepts regarding the nature of mammalian prions. However, from the perspective of structural biology, this parameter is merely a surrogate of structural information, as PK-resistance may be associated with different structural motifs, and may also result from the presence of additional molecules that associate with PrPSc and prevent access of the protease to potential cleavage sites. 

In a directed evolution approach pursued in our laboratories, the sequence specificity of a microbial protease was systematically altered away from its natural substrate to match the activation site of plasminogen... 

Nature Reviews Cancer, Vol. 7, p>p. 800-808, ISSN 1474-1768 Maarten, AJ., Jules, B. (2011) Co-evolution of insect proteases and plant protease inhibitors. 

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