X-ray and cryo-EM structures of inhibitor-bound cytochrome bc1 complexes for structure-based drug discovery

Amporndanai, K.; Johnson, R.M.; O'Neill, P.M.; Fishwick, C.W.G.; Jamson, A.H.; Rawson, S.; Muench, S.P.; Hasnain, S.S.; Antonyuk, S.V.

doi:10.1107/S2052252518001616

Figure 3
Analysis of the Q_i site in the three different cryo-EM maps with the density contoured at 3σ. (a) The Q_i site in the apo bc₁ cryo-EM map shows minimal density (purple mesh) which does not correspond to any side chains or the haem b_L group, suggesting noise within the map or that the natural substrate ubiquinone is bound in a small number of bc₁ molecules. (b) The Q_i site in the cryo-EM map of bc₁–GSK932121. The inhibitor density (green) suggests there are two modes of inhibitor binding, accompanied by rotation around the oxygen–carbon bond. The binding pose shown in green agrees with the crystal structure, with the trifluoromethyl group pointing towards Met194. There is additional density which suggests that the trifluoromethoxyphenyl group could be rotated and point towards Asp228, revealing an additional mode of binding (shown in blue). (c) The Q_i site in the cryo-EM map of bc₁–SCR0911, with the inhibitor shown in pink and located in strong density. The inhibitor is expected to make a hydrogen-bond contact with His201 and strongly fits the density.

IUCrJ

Volume 5| Part 2| March 2018| Pages 200-210

ISSN: 2052-2525

https://doi.org/10.1107/S2052252518001616

CRYO | EM

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