tailieunhanh - Báo cáo khoa học: Staphylococcus aureus elongation factor G – structure and analysis of a target for fusidic acid

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 Staphylo-coccus aureus, but no structural information has been available for EF-G from these species. | ỊFEBS Journal Staphylococcus aureus elongation factor G - structure and analysis of a target for fusidic acid Yang Chen Ravi Kiran Koripella Suparna Sanyal and Maria Selmer Department of Celland Molecular Biology Uppsala University Sweden Keywords antibiotic resistance crystallography elongation factor G EF-G fusidic acid switch region Correspondence M. Selmer Department of Celland Molecular Biology Uppsala University BMC Box 596 751 24 Uppsala Sweden Fax 46 18 536971 Tel 46 18 4714177 E-mail Database The atomic coordinates and observed structure factors are available in the Protein Data Bank database under the accession number 2XEX Received 22 April2010 revised 28 June 2010 accepted 14 July 2010 doi 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 A 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 A 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 .