NDLI: Additivity of mutant effects assessed by binomial mutagenesis.

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Additivity of mutant effects assessed by binomial mutagenesis.

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Additivity of mutant effects assessed by binomial mutagenesis.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Gregoret, L. M. Sauer, R. T.
Description	Author Affiliation: Gregoret LM ( Department of Biology, Massachusetts Institute of Technology, Cambridge 02139.);
Abstract	Eleven amino acid positions in the helix-turn-helix of lambda repressor have been mutagenized by using a combinatorial method in which alanine is substituted at each position with a probability of 0.5. Approximately 25% of the 2048 proteins in the resulting binomial library are active, including some variants with as many as seven alanine substitutions. The frequency of alanine substitutions in the set of active variants is a measure of the importance of the wild-type residue at each mutagenized position, and comparison of the frequencies of pairwise mutations with those expected based upon the single-position frequencies allows the additivity of mutant effects to be tested. For the positions examined here, we find that the effects of multiple substitutions are largely additive and are able to predict the activity class of the binomial mutants with 90% accuracy by using a model that simply sums penalty scores derived from the alanine substitution frequencies. We also find, however, that several residue pairs, including some that are distant in the three-dimensional structure, do display nonadditive effects that appear to be statistically significant.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	9
Volume Number	90
Language	English
Publisher	National Academy of Sciences
Publisher Date	1993-06-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Bacteriophage Lambda Genetics DNA-Binding Proteins Genes, Synthetic Genes, Viral Mutagenesis Mutation Protein Structure, Secondary Repressor Proteins Chemistry Alanine Amino Acid Sequence Cloning, Molecular Genetic Variation Models, Molecular Molecular Sequence Data Plasmids Transcription Factors Viral Proteins Viral Regulatory And Accessory Proteins Comparative Study Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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