Fig. 5: Comparison of 3CLpro interactions with its N-terminal sequence and the hNEMO_226–234 peptide.

a The surface of chain B from our hNEMO_226–234-bound structure is depicted as in Fig. 2c. This is juxtaposed with residues from our structure that form interactions with the hNEMO_226–234 peptide (purple sticks) as well as N-terminal interacting residues (green sticks) from a structure of 3CLpro bound to an N-terminal peptide (PDB_ID:7N89). For 7N89, oxygens are colored light red, nitrogens are colored aquamarine and sulfurs are colored light yellow, for ease of comparison. Residues forming conserved interactions are labeled in black. Those found only in hNEMO_226–234-bound 3CLpro are labeled in purple. Those found only in 7N89 are labeled in green. Water molecules are portrayed as red spheres and are exclusive to 7N89. Leu27 forms a hydrophobic contact with P1’ of hNEMO_226–234 only. Met49 forms a hydrophobic contact with the P2 residues of both hNEMO_226–234 and the N-terminal peptide, but also forms a hydrophobic contact with P3’ of the N-terminal sequence. b Comparison of bound hNEMO_226–234 from our structure with bound N-terminal peptide from 7N89 shows a conserved substrate pose. hNEMO_226–234 is colored as in Fig. 2c. The N-terminal peptide carbons in 7N89 are colored dark brown and the oxygens and nitrogens are colored as in panel a. Substrate residues are labeled P6-P3’.