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• W2022911301 abstract "Protein engineering has as its goals the design and construction of new peptides and proteins with novel binding and catalytic properties. In one approach to protein engineering, new active sites have been introduced into naturally occurring proteins either by site-directed mutagenesis or by chemical modification. Providing that important changes in the tertiary structures do not result from such alterations, at least a portion of the binding site of the original protein should be available for the formation of complexes between the altered enzyme and its substrates. Many examples of active-site mutations have been described, including the generation by us of a cysteine mutant of alkaline phosphatase. A fundamental limitation of the site-directed mutagenesis methodology is that replacements of residues are restricted to the twenty naturally occurring amino acids. The alternative, chemical modification, is difficult to carry out for the specific replacement of one amino acid by another. However, we have shown that through such modification coenzyme analogues can be introduced covalently into appropriate positions in proteins, allowing us to produce semisynthetic enzymes with catalytic activities radically altered from those of their precursor proteins. In another approach to protein engineering efforts have focused on the construction of systems where, as a first approximation, folding can be neglected and the preparation of secondary structural units is the target. Examples of the successful design of biologically active peptides and proteins along such lines, taken from our own work, include molecules mimicking apolipoproteins, toxins, and many hormones. In recent studies we have progressed to the stage where we are starting to combine the two general approaches to protein engineering we have described and are able to construct small enzymes like ribonuclease T1 and its structural analogues." @default.
• W2022911301 created "2016-06-24" @default.
• W2022911301 creator A5040538424 @default.
• W2022911301 date "1988-07-01" @default.
• W2022911301 modified "2023-10-14" @default.
• W2022911301 title "Catalytic Activity of Enzymes Altered at Their Active Sites" @default.
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• W2022911301 doi "https://doi.org/10.1002/anie.198809131" @default.
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