Rational design of antibiotics based on the structural differences in HCOs. (IMAGE)

National Cerebral and Cardiovascular Center

Rational design of antibiotics based on the structural differences in HCOs.

Caption

Figure 1. (A) Deaths from AMR are predicted to rise globally in the next 35 years. (O’Neill J, Chair. Tackling Drug-Resistant Infections Globally: Final Report and Recommendations. London, UK: Review on Antimicrobial Resistance; 2016; p. 1-84.) (B, C) Allosteric sites (red shadow) of mammalian mtHCO (A: PDB 7XMB) and bacterial HCO (B: PDB 6FWF). Helices of subunit I are shown as blue, and a mammalian-specific subunit, COX7C (shown as red), covers the surface of the inhibitor. The other helices are shown in yellow. (D, E) The surface of the allosteric site is distinct from each other (C: mtHCO, D: bacterial HCO), which makes fitting inhibitors to each corresponding site must have a different character/profile. (F) Q275 is a specific Neisseria HCO inhibitor (filled circle), did not inhibit mammalian mtHCO (open circle).

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Nature communications/ National Cerebral and Cardiovascular Center

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