Nearest-neighbor amino acids of specificity-determining residues influence the activity of engineered Cre-type recombinases.

ABSTRACT: The tyrosine-type site-specific DNA recombinase Cre recombines its target site, loxP, with high activity and specificity without cross-recombining the target sites of highly related recombinases. Understanding how Cre achieves this precision is key to be able to rationally engineer site-specific recombinases (SSRs) for genome editing applications. Previous work has revealed key residues for target site selectivity in the Cre/loxP and the related Dre/rox recombinase systems. However, enzymes in which these residues were changed to the respective counterpart only showed weak activity on the foreign target site. Here, we use molecular modeling and dynamics simulation techniques to comprehensively explore the mechanisms by which these residues determine target recognition in the context of the

SUBMITTER: Soni A 

PROVIDER: S-EPMC7438526 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature