Drug design from the cryptic inhibitor envelope

@article{Lee2016DrugDF,
  title={Drug design from the cryptic inhibitor envelope},
  author={C. Lee and Xiaofei Liang and Qinglin Wu and Javaria Najeeb and Jinshi Zhao and Ramesh Gopalaswamy and M. Tit{\'e}cat and F. Sebbane and N. Lema{\^i}tre and E. Toone and P. Zhou},
  journal={Nature Communications},
  year={2016},
  volume={7}
}
Conformational dynamics plays an important role in enzyme catalysis, allosteric regulation of protein functions and assembly of macromolecular complexes. Despite these well-established roles, such information has yet to be exploited for drug design. Here we show by nuclear magnetic resonance spectroscopy that inhibitors of LpxC—an essential enzyme of the lipid A biosynthetic pathway in Gram-negative bacteria and a validated novel antibiotic target—access alternative, minor population states in… Expand
36 Citations
Targeting a hidden site on class A beta-lactamases.
  • 3
Structure, inhibition, and regulation of essential lipid A enzymes.
  • Peng Zhou, Jinshi Zhao
  • Biology, Medicine
  • Biochimica et biophysica acta. Molecular and cell biology of lipids
  • 2017
  • 16
  • PDF
Structural basis of the UDP-diacylglucosamine pyrophosphohydrolase LpxH inhibition by sulfonyl piperazine antibiotics
  • PDF
The role of NMR in leveraging dynamics and entropy in drug design.
  • 2
...
1
2
3
4
...

References

SHOWING 1-10 OF 61 REFERENCES
Structural basis of the promiscuous inhibitor susceptibility of Escherichia coli LpxC.
  • 20
  • PDF
Intrinsic dynamics of an enzyme underlies catalysis
  • 920
Design and synthesis of potent Gram-negative specific LpxC inhibitors.
  • 38
Dynamic activation of an allosteric regulatory protein
  • 311
Mechanism and inhibition of LpxC: an essential zinc-dependent deacetylase of bacterial lipid A synthesis.
  • A. Barb, P. Zhou
  • Biology, Medicine
  • Current pharmaceutical biotechnology
  • 2008
  • 114
  • PDF
Crystal structure of LpxC, a zinc-dependent deacetylase essential for endotoxin biosynthesis
  • 120
  • PDF
...
1
2
3
4
5
...