Genetic studies of the lac repressor. XIV. Analysis of 4000 altered Escherichia coli lac repressors reveals essential and non-essential residues, as well as "spacers" which do not require a specific…

By P. Markiewicz, L. Kleina, C. Cruz, S. Ehret, Jeffrey H. Miller. 1994

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

Citations in the corpus

Better prediction of functional effects for sequence variants (2015, neutral): “We also included data from comprehensive studies of particular proteins, namely LacI repressor from Escherichia coli [31] (4,041 variants) and the HIV-1 protease [32] (336 variants).”
Predicting the functional consequences of non-synonymous single nucleotide polymorphisms: structure-based assessment of amino acid variation. (2001, background): “Several groups have noted a systematic intolerance to mutation in residues that are either extremely conserved in phylogeny or con®ned in their identity to particular classes of amino acid residues.(14) ± 16 Others point to relationships between functional effects and hydrophobicity or residue volum”
SNAP: predict effect of non-synonymous polymorphisms on function (2007, unknown): “These were the mutagenesis data for LacI repressor from Escherichia coli (32), bacteriophage T4 lysozyme (33), and HIV-1 protease (34).”
Mistranslation-induced protein misfolding as a dominant constraint on coding-sequence evolution (2008, unknown): “Roughly 10%–50% of random substitutions disrupt protein function (Guo et al., 2004; Markiewicz et al., 1994), and most loss-of-function mutations appear to be loss-of-folding mutations (Pakula and Sauer, 1989), also shown by large-scale folding and functional assays (Bloom et al., 2006).”
Predicting deleterious amino acid substitutions. (2001, methodology): “SIFT parameters used on the HIV-1 protease and bacteriophage T4 lysozyme data sets were the same as those determined to work well for the LacI mutation data, so analysis can be generalized to”
Ψ-Φ: Exploring the outer limits of bacterial pseudogenes (2004, background): “Comprehensive studies of the lac repressor gene by site-directed mutagenesis showed that about half of the missense substitutions will completely destroy protein function, and that many of these involve radical changes from the original amino acid (Gordon et al. 1988; Kleina and Miller 1990).”
Needles in stacks of needles: finding disease-causal variants in a wealth of genomic data (2011, unknown): “One such source is mutagenesis experiments of individual proteins that generate many possible mutations and assess their function, as has been performed for several bacterial and viral proteins 95–97 .”