A combinatorial histidine scanning library approach to engineer highly pH-dependent protein switches.

ABSTRACT: There is growing interest in the development of protein switches, which are proteins whose function, such as binding a target molecule, can be modulated through environmental triggers. Efforts to engineer highly pH sensitive protein-protein interactions typically rely on the rational introduction of ionizable groups in the protein interface. Such experiments are typically time intensive and often sacrifice the protein's affinity at the permissive pH. The underlying thermodynamics of proton-linkage dictate that the presence of multiple ionizable groups, which undergo a pK(a) change on protein binding, are necessary to result in highly pH-dependent binding. To test this hypothesis, a novel combinatorial histidine library was developed where every possible combination of histidine and wild-ty

SUBMITTER: Murtaugh ML 

PROVIDER: S-EPMC3190156 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature