Molecular recognition of aminoglycoside antibiotics by ribosomal RNA and resistance enzymes: an analysis of x-ray crystal structures.
The potential of RNA molecules to be used as therapeutic targets by small inhibitors is now well established. In this fascinating wide-open field, aminoglycoside antibiotics constitute the most studied family of RNA binding drugs. Within the last three years, several x-ray crystal structures were solved for aminoglycosides complexed to one of their main natural targets in the bacterial cell, the decoding aminoacyl-tRNA site (A site). Other crystallographic structures have revealed the binding modes of aminoglycosides to the three existing types of resistance-associated enzymes. The present review summarizes the various aspects of the molecular recognition of aminoglycosides by these natural RNA or protein receptors. The analysis and the comparisons of the detailed interactions offer insights that are helpful in designing new generations of antibiotics.
Vicens
Quentin
Q
Institut de Biologie Moléculaire et Cellulaire du CNRS, Modélisation et simulations des Acides Nucléiques, UPR 9002, Université Louis Pasteur, 15 rue René Descartes, 67084 Strasbourg Cedex, France.
Westhof
Eric
E
D000617:Aminoglycosides / Q000737:chemistry*; D000900:Anti-Bacterial Agents / Q000737:chemistry*; D001665:Binding Sites; D018360:Crystallography, X-Ray / Q000379:methods*; D004352:Drug Resistance, Microbial; D004798:Enzymes / Q000737:chemistry*; D008956:Models, Chemical; D008958:Models, Molecular; D011485:Protein Binding; D012313:RNA / Q000737:chemistry; D012335:RNA, Ribosomal / Q000737:chemistry*; D012270:Ribosomes / Q000737:chemistry
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D004798:Enzymes; D012335:RNA, Ribosomal; D012313:RNA