ArticleChemistry & biology2003
A specificity switch in selected cre recombinase variants is mediated by macromolecular plasticity and water.
Article in Chemistry & biology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Mechanisms of Cre recombinase synaptic complex assembly and activation illuminated by Cryo-EM.Nucleic acids research · 2022Article
- DNA binding induces aProceedings of the National Academy of Sciences of the United States of America · 2020Article
- Nearest-neighbor amino acids of specificity-determining residues influence the activity of engineered Cre-type recombinases.Scientific reports · 2020Article
- A heterodimer of evolved designer-recombinases precisely excises a human genomic DNA locus.Nucleic acids research · 2020Article
- High-resolution specificity profiling and off-target prediction for site-specific DNA recombinases.Nature communications · 2019Article
- Engineering altered protein-DNA recognition specificity.Nucleic acids research · 2018Review
- Crystal structure of an engineered, HIV-specific recombinase for removal of integrated proviral DNA.Nucleic acids research · 2017Article
- The partitioning and copy number control systems of the selfish yeast plasmid: an optimized molecular design for stable persistence in host cells.Microbiology spectrum · 2014Review
- Protein-DNA binding: complexities and multi-protein codes.Nucleic acids research · 2014Review
- Expanding the scope of site-specific recombinases for genetic and metabolic engineering.Biotechnology and bioengineering · 2014Review
- Enhanced selection for homologous-recombinant embryonic stem cell clones by Cre recombinase-mediated deletion of the positive selection marker.Transgenic research · 2012Article
- Nucleases: diversity of structure, function and mechanism.Quarterly reviews of biophysics · 2011Review
- Spatially directed assembly of a heterotetrameric Cre-Lox synapse restricts recombination specificity.Journal of molecular biology · 2008Article
- Multiple levels of affinity-dependent DNA discrimination in Cre-LoxP recombination.Biochemistry · 2006Article
- Evolution of variants of yeast site-specific recombinase Flp that utilize native genomic sequences as recombination target sites.Nucleic acids research · 2006Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
The basis for the altered DNA specificities of two Cre recombinase variants, obtained by mutation and selection, was revealed by their cocrystal structures. The proteins share similar substitutions but differ in their preferences for the natural LoxP substrate and an engineered substrate that is inactive with wild-type Cre, LoxM7. One variant preferentially recombines LoxM7 and contacts the substituted bases through a hydrated network of novel interlocking protein-DNA contacts. The other variant recognizes both LoxP and LoxM7 utilizing the same DNA backbone contact but different base contacts, facilitated by an unexpected DNA shift. Assisted by water, novel interaction networks can arise from few protein substitutions, suggesting how new DNA binding specificities might evolve. The contributions of macromolecular plasticity and water networks in specific DNA recognition observed here present a challenge for predictive schemes.
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