What is it about?
We report GSK3011724A (DG167) as a binary inhibitor of -ketoacyl-ACP synthase (KasA) in Mycobacterium tuberculosis. We show synergy in vitro and in vivo and provide various crystal structures and biochemical data.
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Why is it important?
We show that two molecules of DG167 bind in two different sites simultaneously which contradicts the work of GSK published earlier.
Perspectives
This was a multi- year project. This work was virtually completed when the GSK paper came out which showed only one molecule of DG167 in the binding pocket. What followed was the classic story of publishing a paper when you have just been beaten to the punch. It bounced around a few journals, reviewers also asked for extensive revisions which took close to a year to complete. As far as we know GSK have not issued a correction of their structure.
Dr Sean Ekins
Collaborations in Chemistry
Read the Original
This page is a summary of: Synergistic Lethality of a Binary Inhibitor of Mycobacterium tuberculosis KasA, mBio, December 2018, ASM Journals,
DOI: 10.1128/mbio.02101-17.
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