ArticleNucleic acids research2010
A unified genetic, computational and experimental framework identifies functionally relevant residues of the homing endonuclease I-BmoI.
Article in Nucleic acids research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed.
- Machine learning reveals sequence and methylation determinants of SaCas9-PAM interactions in bacteria.Nucleic acids research · 2026Article
- Modular determinants of cleavage preference in GIY-YIG nucleases revealed by block-based DNA shuffling and directed evolution.Nucleic acids research · 2026Article
- Genetic Entanglement Enables Ultrastable Biocontainment in the Mammalian Gut.ACS synthetic biology · 2025Article
- Article
- A generalizable Cas9/sgRNA prediction model using machine transfer learning with small high-quality datasets.Nature communications · 2023Article
- Precise DNA cleavage using CRISPR-SpRYgests.Nature biotechnology · 2023Article
- Perpetuating the homing endonuclease life cycle: identification of mutations that modulate and change I-TevI cleavage preference.Nucleic acids research · 2016Article
- Broadening the targeting range of Staphylococcus aureus CRISPR-Cas9 by modifying PAM recognition.Nature biotechnology · 2015Article
- Article
- The monomeric GIY-YIG homing endonuclease I-BmoI uses a molecular anchor and a flexible tether to sequentially nick DNA.Nucleic acids research · 2013Article
- Monomeric site-specific nucleases for genome editing.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Protein sequence alignment analysis by local covariation: coevolution statistics detect benchmark alignment errors.PloS one · 2012Article
- Natural and engineered nicking endonucleases--from cleavage mechanism to engineering of strand-specificity.Nucleic acids research · 2011Review
- Divalent metal ion differentially regulates the sequential nicking reactions of the GIY-YIG homing endonuclease I-BmoI.PloS one · 2011Article
- Estimating the evidence of selection and the reliability of inference in unigenic evolution.Algorithms for molecular biology : AMB · 2010Article
- Identifying and seeing beyond multiple sequence alignment errors using intra-molecular protein covariation.PloS one · 2010Article
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4 authors.
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Abstract
Insight into protein structure and function is best obtained through a synthesis of experimental, structural and bioinformatic data. Here, we outline a framework that we call MUSE (mutual information, unigenic evolution and structure-guided elucidation), which facilitated the identification of previously unknown residues that are relevant for function of the GIY-YIG homing endonuclease I-BmoI. Our approach synthesizes three types of data: mutual information analyses that identify co-evolving residues within the GIY-YIG catalytic domain; a unigenic evolution strategy that identifies hyper- and hypo-mutable residues of I-BmoI; and interpretation of the unigenic and co-evolution data using a homology model. In particular, we identify novel positions within the GIY-YIG domain as functionally important. Proof-of-principle experiments implicate the non-conserved I71 as functionally relevant, with an I71N mutant accumulating a nicked cleavage intermediate. Moreover, many additional positions within the catalytic, linker and C-terminal domains of I-BmoI were implicated as important for function. Our results represent a platform on which to pursue future studies of I-BmoI and other GIY-YIG-containing proteins, and demonstrate that MUSE can successfully identify novel functionally critical residues that would be ignored in a traditional structure-function analysis within an extensively studied small domain of approximately 90 amino acids.
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