Type II NADH:quinone oxidoreductase (NDH-2) is a proposed drug-target of major pathogenic microorganisms such as Mycobacterium tuberculosis and Plasmodium falciparum. Many NDH-2 inhibitors have been identified, but rational drug development is impeded by the lack of information regarding their mode of action and associated inhibitor-bound NDH-2 structure. We have determined the crystal structure of NDH-2 complexed with a quinolone inhibitor 2-heptyl-4-hydroxyquinoline-N-oxide (HQNO). HQNO is nested into the slot-shaped tunnel of the Q-site, in which the quinone-head group is clamped by Q317 and I379 residues, and hydrogen-bonds to FAD. The interaction of HQNO with bacterial NDH-2 is very similar to the native substrate ubiquinone (UQ1) interactions in the yeast Ndi1-UQ1complex structure, suggesting a conserved mechanism for quinone binding. Further, the structural analysis provided insight how modifications of quinolone scaffolds improve potency (e.g. quinolinyl pyrimidine derivatives) and suggests unexplored target space for the rational design of new NDH-2 inhibitors.
Pharmacology, Toxicology and Pharmaceutical Science
4
5%
Immunology and Microbiology
2
3%
Other
4
5%
Unknown
27
34%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 5. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 10 April 2018.
All research outputs
#10,279,739
of 34,411,289 outputs
Outputs from BBA - Bioenergetics
#601
of 1,988 outputs
Outputs of similar age
#126,640
of 371,613 outputs
Outputs of similar age from BBA - Bioenergetics
#6
of 31 outputs
Altmetric has tracked 34,411,289 research outputs across all sources so far. This one has received more attention than most of these and is in the 70th percentile.
So far Altmetric has tracked 1,988 research outputs from this source. They receive a mean Attention Score of 4.8. This one has gotten more attention than average, scoring higher than 69% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 371,613 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 65% of its contemporaries.
We're also able to compare this research output to 31 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 80% of its contemporaries.
