Fig 10. Overview of the effects of Lpro mutations on the different proteolytic activities of Lpro as well as reduction in IFN-β gene transcription.
(A) Standard cartoon view with transparent surface of Lpro bound to E69 inhibitor shown as blue sticks (PDB: 4QBB). Residues which upon mutation were reported to affect Lpro’s structure or function are shown as colored sticks. Green: C51A inactivates Lpro’s catalytic activity; red: I83A or L86A reduce the DUB activity and IFN induction; pink: L92A and L102A reduce affinity for ISG15; orange: C133S reduces affinity for eIF4G; aquamarine: L143A predicted to open substrate binding pocket. Drawings were generated using PyMol. (B) Overview of the effects of introduced mutations on cleavage and/or degradation of host proteins, deISGylase/DUB activity, and their ability to reduce IFN-β gene transcription. Coloring of mutations is consistent with panel A. The activities of the mutations have been scored + +, +, + /–, or–according to the following criteria. + +, activity is similar to wt Lpro; +, moderately reduced activity; + /–, severely impaired activity;–, no activity.