Fig. 6: Binding of the small-molecule polymerisation inhibitor 716 to AAT.
From: High-resolution ex vivo NMR spectroscopy of human Z α1-antitrypsin
a Chemical structure of the inhibitor 71650. b Measurement of the binding affinity of Alexa-488-labelled 716 for M, Z and S AAT using a fluorescence polarisation assay50. c Crystal structure (PDB ID: 7AEL) illustrating the binding site of 71650. d Assigned 1H,13C HMQC spectra (isoleucine region) of [2H, AβIδ1Lδ2Vγ2Mε-13CH3]-labelled recombinant wild-type AAT in the presence and absence of an excess of 716. Asterisks indicate minor peaks arising from sample degradation. e Combined methyl chemical shift changes in recombinant AAT upon 716 binding, \({\Delta}\delta_{{\mathrm{CH}}} = \sqrt {{\Delta}{\delta}_{\mathrm{H}}^2 + \left( {\Delta}\delta_{\mathrm{C}}/4 \right)^2}\), projected on the structure of 716-bound AAT50. The bound 716 ligand is indicated in green. Colouring of secondary structure elements is consistent with Fig. 1b. Source data are provided as a Source Data file.
