Figure 2: APN dynamics in catalysis and CoV recognition.

(a) The active site of the closed, intermediate and open APN during peptide hydrolysis. The active site at domain II (DII, yellow) contains a modeled poly-alanine peptide coordinated to the zinc ion (cyan sphere). Side chains of APN active site residues are shown with sticks, whereas the poly-alanine is shown as a gray surface with residues as sticks (carbons in grey). N-terminal peptide residues (P1-P1′-P2′) are labeled. Nitrogens, blue; oxygens, red; hydrogen bonds are dashed lines. The helices of the ARM repeat (α25-α27) in domain IV (DIV, green) with the phenylalanine residue that contacts the peptide in the closed conformation (Phe893 in pAPN) are labeled. The crystal structure of the poly-alanine bound to the pAPN (PDB code 4HOM) was used to model it in the active site of closed, intermediate and open structures by structural superposition based on domain II. (b) Conformation of the CoV binding cavity at the domain II-IV interface in the closed and open pAPN structures. Structures were superposed based on domain IV. Ribbon diagrams of the open pAPN in complex with the porcine CoV RBD (Supplementary Fig. S1b), with residues that contact the RBD in sticks with carbons in yellow (domain II) and green (domain IV). The same residues are shown for the superposed closed structure (carbons in grey). The RBD motif that penetrates the pAPN cavity is shown with a grey surface and with residues as sticks (carbons in cyan or in magenta for Trp).