Crystal structure of the bacterial ribosomal decoding site complexed with amikacin containing the γ-amino-α-hydroxybutyryl (haba) group

• Published in: Biochimie 2006-08, Vol.88 (8), p.1027-1031
• Main Authors: Kondo, Jiro, François, Boris, Russell, Rupert J.M., Murray, James B., Westhof, Eric
• Format: Article
• Language: English
• Subjects: Amikacin - chemistry; Amikacin - pharmacology; Aminoglycoside; Bacteria; Binding Sites - genetics; Biochemistry, Molecular Biology; Crystallography, X-Ray - methods; Haba group; Life Sciences; Models, Molecular; Nucleic Acid Conformation - drug effects; Oligonucleotides - chemistry; Oligonucleotides - genetics; Ribosomal decoding site; Ribosomes - chemistry; Ribosomes - genetics; Ribosomes - metabolism; RNA, Ribosomal, 16S - chemistry; RNA, Ribosomal, 16S - genetics; RNA, Ribosomal, 16S - metabolism; X-ray analysis
• ISSN: 0300-9084; 1638-6183
• DOI: 10.1016/j.biochi.2006.05.017

Amikacin is the 4,6-linked aminoglycoside modified at position N1 of the 2-deoxystreptamine ring (ring II) by the L-haba group. In the present study, the crystal structure of a complex between oligonucleotide containing the bacterial ribosomal A site and amikacin has been solved at 2.7 Å resolution. Amikacin specifically binds to the A site in practically the same way as its parent compound kanamycin. In addition, the L-haba group interacts with the upper side of the A site through two direct contacts, O2*…H–N4(C1496) and N4*–H…O6(G1497). The present crystal structure shows how the introduction of the L-haba group on ring II of aminoglycoside is an effective mutation for obtaining a higher affinity to the bacterial A site.