Gentamicins structure

Gem, see Geminal, 705 Geminal (gem), 705 Genome, size of in humans. 1107 Gentamicin, structure of, 1002 Geraniol, biosynthesis of, 382 Geranyl diphosphate, biosynthesis of, 1077-1078... 

The solution structures of 1 1 complex between paromomycin and gentamicin Cla and the A-site oligonucleotide have been solved at high resolution using heteronuclear NMR techniques These approaches require the preparation of uniformly labeled N- and C-RNA oligonucleotides via in vitro transcription with labeled nucleoside triphosphates. The use of RNAs labeled with NMR-active nuclei allows for the application of sophisticated heteronuclear NMR methods. These methods facilitate the assigmnent of NMR resonances and the acquisition of structural restraints for detailed structure determinations. 

Figure 5.5. NMR structures of paromomycin and gentamicin Cl a in complex with the A-site oligonucleotide. See text for full caption.

Resistance What the pathogen does to the drug. For example, some strains of Pseudomonas aeruginosa produce a plasmid-mediated adeny-lase that inactivates gentamicin by chemically altering its structure. 

Yoshizawa S, Fourmy D, Puglisi JD (1998) Structural origins of gentamicin antibiotic action. EMBO J 17 6437-6448... 

Structures of several important aminoglycoside antibiotics. Ring II is 2-deoxystreptamine. The resemblance between kanamycin and amikacin and between gentamicin, netilmicin, and tobramycin can be seen. The circled numerals on the kanamycin molecule indicate points of attack of plasmid-mediated bacterial transferase enzymes that can inactivate this drug. , , and , acetyltransferase , phosphotransferase , adenylyltransferase. Amikacin is resistant to modification at , , , and . 

Most aminoglycosides are complexes of several almost identical components differing either in the degree of methylation of one amino sugar unit, as in the case of gentamicin, or in the stereochemistry of the disaccharide unit, as in the case of neomycin. Differences in the substitutions on the basic ring structures between the various aminoglycosides account for the relatively minor differences in antimicrobial spectra, patterns of resistance, and toxicity. 

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