, 2006; Sawaya and Kraut, 1997; Figure 1—figure complement 1), we expected the mutational landscape of DHFR for being constrained because of the necessity to adopt these distinct conformations. Also, prior do the job had prompt DHFR is impacted by cellular constraints for example protein high-quality Regulate (Bershtein et al., 2013) along with the Make-up of the poisonous metabolic intermediate (Schober et al., 2019). We hence anticipated deep mutational scanning to expose a extremely constrained mutational landscape for DHFR that will contrast Using the mutational tolerance observed in other devices.
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