Local and Global Breathing Motions Prime the Access to Buried Binding Site in an Antibiotic-Sequestering Protein.

ABSTRACT: Proteins frequently undergo large-scale conformational excursions in their native ensemble. Such structural transitions are particularly critical for enabling access to binding sites when they are buried in the protein interior. Here, we map the conformational landscape of AlbAS, a natural isoform of the transcription factor AlbA from the gut microbe Klebsiella oxytoca, which sequesters the antibiotic albicidin in a solvent-inaccessible binding tunnel. Combining equilibrium, time-resolved experiments, structural mass spectrometry and calorimetry with statistical modeling, we show that AlbAS displays large differences in local and global stability and dynamics, with ∼600-fold difference in unfolding rates across different parts of the structure. Several residues lining the ligand-bin

SUBMITTER: Natarajan L 

PROVIDER: S-EPMC12531866 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature