The chemistry of aurodox and related antibiotics

Maehr, Hubert; Leach, Michael; Williams, Thomas H.; Blount, John F.

doi:10.1139/v80-080

Cited by 54 publications

(21 citation statements)

References 18 publications

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“…Preparation of the Ternary Complex EF-Tu⅐GDP⅐Aurodox-Since aurodox was reported to be moderately sensitive to light (21), exposure was kept at a minimum. Because of its extremely low solubility in water, a 120 mM alcoholic solution was prepared.…”

Section: Methodsmentioning

confidence: 99%

Conformational Change of Elongation Factor Tu (EF-Tu) Induced by Antibiotic Binding

Vogeley¹,

Palm²,

Mesters³

et al. 2001

Journal of Biological Chemistry

111

114

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Aurodox is a member of the family of kirromycin antibiotics, which inhibit protein biosynthesis by binding to elongation factor Tu (EF-Tu). We have determined the crystal structure of the 1:1:1 complex of Thermus thermophilus EF-Tu with GDP and aurodox to 2.0-Å resolution. During its catalytic cycle, EF-Tu adopts two strikingly different conformations depending on the nucleotide bound: the GDP form and the GTP form. In the present structure, a GTP complex-like conformation of EF-Tu is observed, although GDP is bound to the nucleotide-binding site. This is consistent with previous proposals that aurodox fixes EF-Tu on the ribosome by locking it in its GTP form. Binding of EF-Tu⅐GDP to aminoacyl-tRNA and mutually exclusive binding of kirromycin and elongation factor Ts to EF-Tu can be explained on the basis of the structure. For many previously observed mutations that provide resistance to kirromycin, it can now be understood how they prevent interaction with the antibiotic. An unexpected feature of the structure is the reorientation of the His-85 side chain toward the nucleotide-binding site. We propose that this residue stabilizes the transition state of GTP hydrolysis, explaining the acceleration of the reaction by kirromycin-type antibiotics.

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Section: Methodsmentioning

confidence: 99%

Conformational Change of Elongation Factor Tu (EF-Tu) Induced by Antibiotic Binding

Vogeley¹,

Palm²,

Mesters³

et al. 2001

Journal of Biological Chemistry

111

114

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“…[388][389][390][391][392][393][394][395][396][397][398][399][400][401] For 228 and some other congeners it was shown that the activity relies on an inhibition of elongation factor Tu (EF-Tu), [402][403][404][405][406] which plays a key role in protein biosynthesis by mediating the entry of aminoacyl-tRNAs into the ribosome. [407][408][409] For this reason, the name elfamycins was proposed for this compound family.…”

Section: Kirromycinmentioning

confidence: 99%

Biosynthesis of polyketides by trans-AT polyketide synthases

2010

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“…Interestingly, a total of nine compounds, including a novel compound 1, were purified from the culture of NBRC 105896. These include indolactam V, 20 mocimycin, 21 5,6-dihydromocimycin, 22 N-demethylteleocidin A 1 , 23 1 and teleocidin A 1 24 from the mycelial extract, and factumycin 25 and kirrothricin 22 from the supernatant extract of the culture. Levorin A 2 26 was also detected in the culture grown in a production medium containing 1% HP-20 (Mitsubishi Chemical, Tokyo, Japan).…”

mentioning

confidence: 99%