2bm1
From Proteopedia
| Line 4: | Line 4: | ||
==Overview== | ==Overview== | ||
| - | Fusidic acid (FA) is a steroid antibiotic commonly used against Gram | + | 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. |
==About this Structure== | ==About this Structure== | ||
| Line 13: | Line 13: | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Thermus thermophilus]] | [[Category: Thermus thermophilus]] | ||
| - | [[Category: Gudkov, A | + | [[Category: Gudkov, A T.]] |
[[Category: Hansson, S.]] | [[Category: Hansson, S.]] | ||
[[Category: Liljas, A.]] | [[Category: Liljas, A.]] | ||
| - | [[Category: Logan, D | + | [[Category: Logan, D T.]] |
[[Category: Singh, R.]] | [[Category: Singh, R.]] | ||
[[Category: GDP]] | [[Category: GDP]] | ||
| Line 27: | Line 27: | ||
[[Category: translation]] | [[Category: translation]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:39:14 2008'' |
Revision as of 14:39, 21 February 2008
|
RIBOSOMAL ELONGATION FACTOR G (EF-G) FUSIDIC ACID RESISTANT MUTANT G16V
Overview
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.
About this Structure
2BM1 is a Single protein structure of sequence from Thermus thermophilus with and as ligands. Known structural/functional Site: . Full crystallographic information is available from OCA.
Reference
Structural insights into fusidic acid resistance and sensitivity in EF-G., Hansson S, Singh R, Gudkov AT, Liljas A, Logan DT, J Mol Biol. 2005 May 13;348(4):939-49. PMID:15843024
Page seeded by OCA on Thu Feb 21 16:39:14 2008
