3zzu | pdb_00003zzu

Crystal structure of Staphylococcus aureus elongation factor G with mutations M16I and F88L

spinqualitylabelsall models 3zzu, resolution 2.98Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3zzu is a 2 chain structure with sequence from Staphylococcus aureus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.98Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function EFG_STAAU Catalyzes the GTP-dependent ribosomal translocation step during translation elongation. During this step, the ribosome changes from the pre-translocational (PRE) to the post-translocational (POST) state as the newly formed A-site-bound peptidyl-tRNA and P-site-bound deacylated tRNA move to the P and E sites, respectively. Catalyzes the coordinated movement of the two tRNA molecules, the mRNA and conformational changes in the ribosome.[HAMAP-Rule:MF_00054_B] Publication Abstract from PubMed Antibiotic resistance in bacteria is often associated with fitness loss, which is compensated by secondary mutations. Fusidic acid (FA), an antibiotic used against pathogenic bacteria Staphylococcus aureus, locks elongation factor-G (EF-G) to the ribosome after GTP hydrolysis. To clarify the mechanism of fitness loss and compensation in relation to FA resistance, we have characterized three S. aureus EF-G mutants with fast kinetics and crystal structures. Our results show that a significantly slower tRNA translocation and ribosome recycling, plus increased peptidyl-tRNA drop-off are the causes for fitness defect of the primary FA-resistant mutant F88L. The double mutant F88L+M16I is three to four times faster than F88L in both reactions and showed no tRNA drop-off; explaining its fitness compensatory phenotype. The M16I mutation alone showed hypersensitivity to FA, higher activity and somewhat increased affinity to GTP. The crystal structures demonstrate that F88 in switch II is a key residue for FA locking and also for triggering inter-domain movements in EF-G essential for its function, explaining functional deficiencies in F88L. The mutation M16I loosens the hydrophobic core in the G domain and affects domain I to domain II contact, resulting in improved activity both in the wild-type and F88L background. Thus, FA resistant EF-G mutations causing fitness loss and compensation operate by affecting the conformational dynamics of EF-G on the ribosome. Mechanism of elongation factor-G mediated fusidic acid resistance and fitness compensation in Staphylococcus aureus.,Koripella RK, Chen Y, Peisker K, Koh CS, Selmer M, Sanyal S J Biol Chem. 2012 Jul 5. PMID:22767604 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Elongation factor 3D structures

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