Fig. 5: α₁AT binds the extracellular region of TMPRSS2 and inhibits TMPRSS2 protease activity.

a Protein–protein docking analysis of a homology model for the TMPRSS2 extracellular fragment (green, PDB 1z8g) and α₁AT (gray, PDB 3cwm) and computationally calculated binding free energy (ΔG_calc) of the complex. b Detailed view on α₁AT-TMPRSS2 binding interface. The sidechains of α₁AT (gray) residues are represented with sticks, while sidechains of TMPRSS2 (green) are shown with balls and sticks. Hydrogen atoms are omitted for clarity, carbon, oxygen, nitrogen or sulfur atoms of amino acid side chains depicted in light blue, red, dark blue or yellow, respectively. The hydrophobic patch near the TMPRSS2 catalytic triad is highlighted with a green transparent surface. c α₁AT inhibits cell-associated TMPRSS2 activity. HEK293T cells were transfected with a TMPRSS2 expression plasmid and treated with Prolastin (α₁AT, blue), camostat mesylate (CM, gray) or E-64d (green) followed by incubation with the fluorogenic TMRPSS2 protease substrate BOC-Gln-Ala-Arg-AMC. Graph shows the relative area under the curve analysis of fluorescence intensities over 2 h that were corrected by values for mock-transfected HEK293T cells. d α₁AT inhibits recombinant TMPRSS2 enzyme activity. Recombinant human TMPRSS2 was mixed with Prolastin (α₁AT, blue) or CM (gray) prior to addition of fluorogenic TMPRSS2 protease substrate BOC-Gln-Ala-Arg-AMC, graph shows relative fluorescence intensities after 3 h of incubation. The mean ± SEM of n = 2 (c) or n = 3 (d) independent experiments in biological duplicates are shown (ordinary one-way ANOVA with Dunett´s multiple comparison test). Source data are provided as a Source data file.