1d8t

CRYSTAL STRUCTURE OF ELONGATION FACTOR, TU (EF-TU-MGGDP) COMPLEXED WITH GE2270A, A THIAZOLYL PEPTIDE ANTIBIOTIC

spinqualitylabelsall models 1d8t, resolution 2.35Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1d8t is a 4 chain structure with sequence from Escherichia coli and Planobispora rosea. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ACT, GDP, MG NonStd Res: BB6, BB7, BB8, BB9, MEN, MH6, NH2 Related: 1e9w, 1oln, 2c77, 2jq7, 2zjp, 3cf5 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [THCL_PLARO] Has bacteriocidal activity against Gram-positive bacteria and a few Gram-negative bacteria. It is particularly active against anaerobes. Inhibits bacterial protein biosynthesis by preventing the formation of a stable complex between the elongation factor Tu (EF-Tu), GTP and tRNA, hindering the activation of EF-Tu. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed The structure of a 1:1 molar complex between Escherichia coli elongation factor (EF) Tu-GDP and the cyclic thiazolyl peptide antibiotic, GE2270A, has been determined by X-ray diffraction analysis to a resolution of 2.35 A and refined to a crystallographic refinement factor of 20.6%. The antibiotic binds in the second domain of EF-Tu-GDP, making contact with three segments of amino acids (residues 215-230, 256-264, and 273-277). The majority of the protein-antibiotic contacts are van der Waals interactions. A striking feature of the antibiotic binding site is the presence of a salt bridge, not previously observed in other EF-Tu complexes. The ionic interaction between Arg 223 and Glu 259 forms over the antibiotic and probably accounts for the strong affinity observed between EF-Tu and GE2270A. Arg 223 and Glu 259 are highly conserved, but not invariant throughout the prokaryotic EF-Tu family, suggesting that the antibiotic may bind EF-Tu from some organisms better than others may. Superposition of the antibiotic binding site on the EF-Tu-GTP conformation reveals that one region of the antibiotic would form steric clashes with the guanine nucleotide-binding domain in the GTP, but not the GDP, conformation. Another region of the antibiotic binds to the same site as the aminoacyl group of tRNA. Together with prior biochemical studies, the structural findings confirm that GE2270A inhibits protein synthesis by blocking the GDP to GTP conformational change and by directly competing with aminoacyl-tRNA for the same binding site on EF-Tu. In each of the bacterial strains that are resistant to GE2270A, the effect of a site-specific mutation in EF-Tu could explain resistance. Comparison of the GE2270A site in EF-Tu with sequence homologues, EF-G and EF-1alpha, suggests steric clashes that would prevent the antibiotic from binding to translocation factors or to the eukaryotic equivalent of EF-Tu. Although GE2270A is a potent antibiotic, its clinical efficacy is limited by its low aqueous solubility. The results presented here provide the details necessary to enhance the solubility of GE2270A without disrupting its inhibitory properties. Structure of an EF-Tu complex with a thiazolyl peptide antibiotic determined at 2.35 A resolution: atomic basis for GE2270A inhibition of EF-Tu.,Heffron SE, Jurnak F Biochemistry. 2000 Jan 11;39(1):37-45. PMID:10625477 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Elongation factor 3D structures

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