Crystal structure of the bacterial ribosomal decoding site complexed with amikacin containing the gamma-amino-alpha-hydroxybutyryl (haba) group.
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 A 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.
Kondo
Jiro
J
Institut de Biologie Moléculaire et Cellulaire, UPR9002 CNRS, Université Louis-Pasteur, 15, rue René-Descartes, 67084 Strasbourg, France.
François
Boris
B
Russell
Rupert J M
RJ
Murray
James B
JB
Westhof
Eric
E
D000583:Amikacin / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites / Q000235:genetics; D018360:Crystallography, X-Ray / Q000379:methods; D008958:Models, Molecular; D009690:Nucleic Acid Conformation / Q000187:drug effects; D009841:Oligonucleotides / Q000737:chemistry* / Q000235:genetics; D012336:RNA, Ribosomal, 16S / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D012270:Ribosomes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D009841:Oligonucleotides; D012336:RNA, Ribosomal, 16S; D000583:Amikacin