Slack / Private Message Drop — page 340

N417K [2020-12-22 14:18:26] [Robert Garry] [thread - ID: 2020-12-22 10:33:47] @Kristian Andersen And since you corrected me -thx - the N417K could contribute to enhanced receptor binding. K binding better to D. [2020-12-22 14:18:28] [Robert Garry] Actually it is K417N - so not likely to help with receptor binding. [2020-12-22 14:40:26] [Robert Garry] [thread - ID: 2020-12-22 10:33:47] @Kristian Andersen Wait - take the beer back it is actually K417N. [2020-12-22 14:44:27] [Robert Garry] shared file(s): image.png [2020-12-22 15:21:19] [Robert Garry] [thread - ID: 2020-12-22 10:33:47] @Kristian Andersen Here making a big deal about K417 salt bridge to D30: https://www.pnas.org/content/117/25/13967 [2020-12-22 17:55:37] [Robert Garry] However , Starr2020 says K417N actually increases binding so maybe a positive. [2020-12-22 18:28:28] [Eddie Holmes] Thanks for doing all this chaps. I'll need to see if I can get my head around it all. [2020-12-23 03:46:00] [Robert Garry] Cliff Notes version: [2020-12-23 03:51:44] [Robert Garry] Two RBD residues (residues 479 and 487) had to mutate to enable civet SC1 (the 99+% virus) to jump to humans. These changes allow interaction with contact residues on human ACE2. JVI paper sums it nicely. This happened more than once with SC1. [2020-12-23 03:53:32] [Robert Garry] The two SC1 residues are equivalent in how they interact with ACE2 to to SC2 RBD residues Q493 and N501. [2020-12-23 03:58:37] [Robert Garry] Two interspecies transfers of SC2 have occurred. Human to mouse in the lab. Human to mink and back on the fur farms. Residues Q493 and N501 are also involved. N501Y enables replication of SC2 in mice; Q493H makes the mouse adapted SC2 pathogenic prob by increasing replication. A SC2 Q493K change can increase both replication and pathogenesis in mice.