2BM0

Ribosomal elongation factor G (EF-G) Fusidic acid resistant mutant T84A

Summary for 2BM0

• Entry DOI: 10.2210/pdb2bm0/pdb
• Related: 1DAR 1EFG 1ELO 1FNM 1IP8 1IPM 1IPO 1IPR 1JQM 1JQS 1KTV 1PN6 2BM1 2EFG
• Descriptor: ELONGATION FACTOR G, GUANOSINE-5'-DIPHOSPHATE, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: switch ii, elongation factor, gtp-binding, translation mutation thr84ala, protein biosynthesis
• Biological source: THERMUS THERMOPHILUS
• Cellular location: Cytoplasm: P13551
• Total number of polymer chains: 1
• Total formula weight: 77428.61

Authors

Hansson, S.,Singh, R.,Gudkov, A.T.,Liljas, A.,Logan, D.T. (deposition date: 2005-03-09, release date: 2005-05-04, Last modification date: 2023-12-13)

Primary citation

Hansson, S.,Singh, R.,Gudkov, A.T.,Liljas, A.,Logan, D.T.
Structural Insights Into Fusidic Acid Resistance and Sensitivity in EF-G
J.Mol.Biol., 348:939-, 2005

PubMed Abstract: Fusidic acid (FA) is a steroid antibiotic commonly used against Gram positive bacterial infections. It inhibits protein synthesis by stalling elongation factor G (EF-G) on the ribosome after translocation. A significant number of the mutations conferring strong FA resistance have been mapped at the interfaces between domains G, III and V of EF-G. However, direct information on how such mutations affect the structure has hitherto not been available. Here we present the crystal structures of two mutants of Thermus thermophilus EF-G, G16V and T84A, which exhibit FA hypersensitivity and resistance in vitro, respectively. These mutants also have higher and lower affinity for GTP respectively than wild-type EF-G. The mutations cause significant conformational changes in the switch II loop that have opposite effects on the position of a key residue, Phe90, which undergoes large conformational changes. This correlates with the importance of Phe90 in FA sensitivity reported in previous studies. These structures substantiate the importance of the domain G/domain III/domain V interfaces as a key component of the FA binding site. The mutations also cause subtle changes in the environment of the "P-loop lysine", Lys25. This led us to examine the conformation of the equivalent residue in all structures of translational GTPases, which revealed that EF-G and eEF2 form a group separate from the others and suggested that the role of Lys25 may be different in the two groups.

PubMed: 15843024
DOI: 10.1016/J.JMB.2005.02.066

Experimental method

X-RAY DIFFRACTION (2.4 Å)