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Staphylococcus aure...
Staphylococcus aureus elongation factor G - structure and analysis of a target for fusidic acid
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- Chen, Yang (author)
- Uppsala universitet,Institutionen för cell- och molekylärbiologi
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- Koripella, Ravi Kiran (author)
- Uppsala universitet,Institutionen för cell- och molekylärbiologi
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- Sanyal, Suparna (author)
- Uppsala universitet,Institutionen för cell- och molekylärbiologi
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- Selmer, Maria (author)
- Uppsala universitet,Institutionen för cell- och molekylärbiologi
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(creator_code:org_t)
- 2010-08-13
- 2010
- English.
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In: The FEBS Journal. - : Wiley. - 1742-464X .- 1742-4658. ; 277:18, s. 3789-3803
- Related links:
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https://febs.onlinel...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- 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 1.9 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 fusA-based fusidic acid resistance mutations in the light of the new structure of EF-G from S. aureus, and a recent structure of T. thermophilus EF-G in complex with the 70S ribosome with fusidic acid [Gao YG et al. (2009) Science326, 694-699]. The mutations can be classified as affecting FA binding, EF-G-ribosome interactions, EF-G conformation, and EF-G stability.
Subject headings
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
Keyword
- antibiotic resistance
- crystallography
- elongation factor G (EF-G)
- fusidic acid
- switch region
- Biology
- Biologi
Publication and Content Type
- ref (subject category)
- art (subject category)
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