Crystal structure, conformation, and absolute configuration of kanamycin A

Kanamycin, an antibiotic complex produced by Streptomyces kanamycetius isolated from Japanese soil, was described by Okami and Umezawa as early as 1957 and consists of three components: Kanamycin A (the major component), B, and C. The disulfate salt of kanamycin A [4-O-(6-amino-6-deoxy-alpha-D-glucopyranosyl)-6-O-(3-amino-3-deoxy-alpha-D-glucopyranosyl)-2-deoxystreptamine] is a broad-spectrum antibiotic that is used to treat gonorrhea, salmonella, tuberculosis, and many other diseases. Crystals of kanamycin A monosulfate monohydrate obtained from water are triclinic, space group P1, with a = 7.2294(14), b = 12.4922(15), c = 7.1168(9), a = 94.74(1), beta = 89.16(1), gamma = 91.59(1), V= 640.2(2) angstrom(3), mu(CuK alpha) = 18.4 cm(-1), FW 600.6, D-calc = 1.558 g/cm(3), CAD-4 diffractometric data (2693 reflections, 2554 >= 3 sigma(I)), structure by SHELX-86 and refined by full-matrix least squares to a final R value of 0.038. The wrong conformer had an R value of 0.043. Both of the D-glucose moieties are attached to the deoxystreptamine by alpha linkages. This absolute configuration agrees with the earlier determination by both chemical and X-ray methods with photographic data. The (0, 0) values for the glycosidic linkages are 101.6 degrees, -121.1 degrees, 106.3 degrees, and -140.4 degrees, respectively. Kanamycin interacts with the ribosomal S 12 protein to stabilize the codon-anticodon binding between mRNA and the aminoacyl tRNA and inhibits the elongation of peptide chains through a series of reactions resulting in the prevention of ribosomes from moving along mRNA.