Fig. 5: The loop conformational ensemble is altered by ligand-binding to the active site.
From: Functional control of a 0.5 MDa TET aminopeptidase by a flexible loop revealed by MAS NMR
a Chemical structure of the inhibitor peptide amastatin. b Structural view of amastatin in the active site (PDB: 1Y0Y; loops modeled with SwissModel). c 1H-13C correlation spectrum of WT TET2 in the absence and presence of the inhibitor amastatin, showing a clear change of the peak of the loop residue V120. The dashed arrow indicates the putative shift of the V120 cross-peak to a new position. The shift of the cross-peak of V251 is ascribed to effects from direct binding of amastatin. d Equivalent 1H-13C spectra of H123F TET2 in the apo and amastatin-bound states. The unchanged peak position and intensity of V120 indicates that the loop ensemble is not altered by amastatin, despite full occupancy of the active site with amastatin (Supplementary Figure 15). The full spectra are shown in Supplementary Figure 16. e Schematic representation of the loop conformational ensemble, and the impact of ligands in the active site on reweighting populations within the ensemble.
