Open mattodd opened 2 years ago
Update by email from Becca May 12th "This week I have run a competition assay with Dana’s compound 759 to try and determine the mode of inhibition it is having on the Mur ligases.
From this assay system, it appears that 759 is acting in a non-competitive manner to ATP. To get a clearer picture of whether it is still binding in the pocket adjacent to the ATP binding site, or somewhere else on the enzyme we will still need crystallography.
Hope this helps to start answering the question of where these compounds are binding. "
Very interesting, have requested data.
Hopefully the attached is useful. Best Wishes, Adrian
Date: June 14th 2022 Time: 2pm UK time (other times)
Place: https://ucl.zoom.us/j/91379419977
Recording: https://youtu.be/FeKllES0QaU Previous Meeting: #75
Apologies: Decks: Please remember that if you share slides/info, to drag and drop those into a comment on this page, below.
Agenda:
1) Elaborated Fragments Inhibiting Two Murs
2) Atomwise Hits
3) Variants of AZ Compounds
4) New Protein Structures
As per update from Jan Abendroth in #80, new structures obtained for MurD + UMA?
Do we need to consider the importance of the observed carbamoylation of a residue (Lys198 (-> KCX198) in a structure (7TI7). Does this influence inhibitor design? See @eyermanncj's analysis, or can this be mothballed?
A discussion of the possible value of truncated structures will be had as part of the Soak-In (being scheduled by @mattodd)
5) De Novo Computational Modelling
Competition launched and is live at #69.
Note @LauraDS1 @Rebecca-Steventon there is a live question for you here from @gemmaTuron.
@Yuhang-CADD to report on progress towards @jhjensen2's originally-suggested compounds (last update was here)
6) Other Potential Starting Points
7) Misc/AOB
8) List of Raw Data That Needs Posting Online
Suitable locations: ideally an electronic lab notebook, another suitable repository (Zenodo, Figshare) or Github itself.
9) Mothballs (if no actions then these need to be linked in wiki and closed)
Next Meeting
July 12th 2pm UK time