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Staphylococcus aureus elongation factor G – structure and analysis of a target for fusidic acid
Author(s) -
Chen Yang,
Koripella Ravi Kiran,
Sanyal Suparna,
Selmer Maria
Publication year - 2010
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2010.07780.x
Subject(s) - fusidic acid , staphylococcus aureus , microbiology and biotechnology , elongation , staphylococcal infections , elongation factor , biology , bacteria , genetics , materials science , rna , ribosome , gene , metallurgy , ultimate tensile strength
Fusidic acid (FA) is a bacteriostatic antibiotic that locks elongation factor G (EF‐G) on the ribosome in a post‐translocational state. It is used clinically against Gram‐positive bacteria such as pathogenic strains of Staphylococcus aureus , but no structural information has been available for EF‐G from these species. We have solved the apo crystal structure of EF‐G from S. aureus to 1.9 Å resolution. This structure shows a dramatically different overall conformation from previous structures of EF‐G, although the individual domains are highly similar. Between the different structures of free or ribosome‐bound EF‐G, domains III–V move relative to domains I–II, resulting in a displacement of the tip of domain IV relative to domain G. In S. aureus EF‐G, this displacement is about 25 Å relative to structures of Thermus thermophilus EF‐G in a direction perpendicular to that in previous observations. Part of the switch I region (residues 46–56) is ordered in a helix, and has a distinct conformation as compared with structures of EF‐Tu in the GDP and GTP states. Also, the switch II region shows a new conformation, which, as in other structures of free EF‐G, is incompatible with FA binding. We have analysed and discussed all known fusA ‐based fusidic acid resistance mutations in the light of the new structure of EF‐G from S. aureus , and a recent structure of T. thermophilus EF‐G in complex with the 70S ribosome with fusidic acid [Gao YG et al. (2009) Science 326 , 694–699]. The mutations can be classified as affecting FA binding, EF‐G–ribosome interactions, EF‐G conformation, and EF‐G stability.