Thursday, April 4, 2013
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and toxic compound extrusion (MATE)-family
transporters to guide inhibitor development
of a MATE-family transporter could guide the rational design of inhibitors
that circumvent drug resistance mediated by the protein. MATE transporters
are conserved from bacteria to humans and export diverse chemical substrates
including antibiotics. A MATE transporter from Pyrococcus furiosus was
crystallized in multiple conformations including with the fluoroquinolone
or thioether-macrocyclic peptide inhibitors. The structure was used to model
the mechanism by which the transporter exports its substrates and imports
cations. Next steps include conducting structural studies of MATE
transporters from pathogenic bacteria and humans and optimizing the drug-like
properties of thioether-macrocyclic peptide inhibitors.
Inc. discovers macrocyclic peptides against targets
designated by its partners.
SciBX 6(13); doi:10.1038/scibx.2013.322
Published online April 4, 2013
Patent application filed;
exclusively licensed to PeptiDream
Tanaka, Y. et al. Nature;
published online March 27, 2013;
Contact: Osamu Nureki, The University of Tokyo, Tokyo, Japan
Contact: Hiroaki Suga, same affiliation as above
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