2bm1
From Proteopedia
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==Overview== | ==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, .. | + | 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== | ||
| - | 2BM1 is a | + | 2BM1 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Thermus_thermophilus Thermus thermophilus] with MG and GDP as [http://en.wikipedia.org/wiki/ligands ligands]. Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2BM1 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: translation]] | [[Category: translation]] | ||
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 13:44:04 2007'' |
Revision as of 11:38, 5 November 2007
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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 MG and GDP as ligands. Structure known Active Site: AC1. 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
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