Fig. 5: Structures of PmIleRS1 and PmIleRS2 bound to mupirocin. | Nature Communications

Fig. 5: Structures of PmIleRS1 and PmIleRS2 bound to mupirocin.

From: Antibiotic hyper-resistance in a class I aminoacyl-tRNA synthetase with altered active site signature motif

Fig. 5

a Mupirocin is an ester of monic acid A and 9-hydroxynonanoic acid. Within the active sites of IleRS1 and IleRS2, the monic acid part mimics the Ile-AMP interactions, whilst the nonanoic acid part is oriented towards the KMSKS loop. b, c In IleRS1, unique interactions with mupirocin include the carboxyl group of the nonanoic acid moiety, which establishes an H-bond with the backbone NH of K597 in the KMSKS loop, the hydrogen bonds between the monic acid part and a proline and an asparagine and stacking interactions of phenylalanine. All interactions are depicted in Supplementary Fig. 11. The position of the HXGH motif remains unaltered upon mupirocin binding. d, e In the IleRS2 active site, mupirocin binds via a lower number of interactions, providing the basis for resistance. Stabilization of the nonanoic carboxylate by H-bonding is precluded by a closed conformation of the KMSKS loop, thereby forcing the nonanoic acid moiety into the cleft between the HXGH motif and the KMSKS loop. As a result, the HXGH motif is pushed away from the KMSKS loop.

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