Abstract
Crystals of recombinant NovP (subunit MW = 29 967 Da; 262 amino acids), an S-adenosyl-L-methionine-dependent O-methyltransferase from Streptomyces spheroides, were grown by vapour diffusion. The protein crystallized in space group P2, with unit-cell parameters a = 51.81, b = 46.04, c = 61.22 A, beta = 104.97 degrees. Native data to a maximum resolution of 1.4 A were collected from a single crystal at the synchrotron. NovP is involved in the biosynthesis of the aminocoumarin antibiotic novobiocin that targets the essential bacterial enzyme DNA gyrase.
Highlights
The aminocoumarin antibiotics competitively inhibit the ATPase activity of DNA gyrase, a validated drug target (Maxwell, 1997; Maxwell & Lawson, 2003), and have considerable therapeutic potential
The three main compounds novobiocin, clorobiocin and coumermycin A1 share common structural features, namely a 3-amino-4,7-dihydroxycoumarin moiety, an l-noviosyl sugar and an aromatic acyl component attached to the amino group of the aminocoumarin moiety
We report the crystallization and preliminary X-ray analysis of NovP, an S-adenosyl-l-methionine-dependent O-methyltransferase from Streptomyces spheroides responsible for the methylation of the 40-hydroxyl group of the noviose sugar, which represents the penultimate step in novobiocin biosynthesis (Freel Meyers et al, 2004)
Summary
The aminocoumarin antibiotics competitively inhibit the ATPase activity of DNA gyrase, a validated drug target (Maxwell, 1997; Maxwell & Lawson, 2003), and have considerable therapeutic potential. The three main compounds novobiocin, clorobiocin and coumermycin A1 share common structural features, namely a 3-amino-4,7-dihydroxycoumarin moiety, an l-noviosyl sugar and an aromatic acyl component attached to the amino group of the aminocoumarin moiety. Crystallographic studies on aminocoumarin complexes of DNA gyrase (Lewis et al, 1996; Holdgate et al, 1997; Tsai et al, 1997) have shown that methyl groups form important hydrophobic interactions with the target enzyme and may have profound effects on the potency of these antibiotics. We report the crystallization and preliminary X-ray analysis of NovP, an S-adenosyl-l-methionine-dependent O-methyltransferase from Streptomyces spheroides responsible for the methylation of the 40-hydroxyl group of the noviose sugar, which represents the penultimate step in novobiocin biosynthesis (Freel Meyers et al, 2004)
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