Sequence-specific recognition of the major groove of RNA by deoxystreptamine.
Aminoglycoside antibiotics specifically interact with a variety of RNA sequences, and in particular with the decoding region of 16S ribosomal RNA in the aminoacyl tRNA acceptor site (A-site). Ring II of aminoglycosides (2-deoxystreptamine) is the most conserved element among aminoglycoside antibiotics that bind to the A-site. NMR structures of aminoglycoside-A-site RNA complexes suggested that the 2-deoxystreptamine core of aminoglycosides specifically recognizes (5')G-U(3') and potentially (5')G-G(3') or (5')U-G(3') steps in the major groove of RNA. Here, we show that isolated deoxystreptamine specifically interacts with G-U steps within the major groove of the A-site RNA. The bulge residue of A-site RNA is required to open the major groove for accommodation of deoxystreptamine. The chemical groups of deoxystreptamine presented to the RNA by the framework of the 6-carbon ring modulate RNA recognition.
Yoshizawa
Satoko
S
Department of Structural Biology, Stanford University School of Medicine, Stanford, California 94305-5126, USA.
Fourmy
Dominique
D
Eason
Robert G
RG
Puglisi
Joseph D
JD
D000900:Anti-Bacterial Agents / Q000737:chemistry*; D001483:Base Sequence; D001665:Binding Sites; D005839:Gentamicins / Q000737:chemistry; D006147:Guanine / Q000737:chemistry; D006595:Hexosamines / Q000737:chemistry*; D006860:Hydrogen Bonding; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010303:Paromomycin / Q000737:chemistry; D012336:RNA, Ribosomal, 16S / Q000737:chemistry*; D014529:Uridine / Q000737:chemistry
D000900:Anti-Bacterial Agents; D005839:Gentamicins; D006595:Hexosamines; D012336:RNA, Ribosomal, 16S; C100093:gentamicin C; D006147:Guanine; D010303:Paromomycin; C007265:2-deoxystreptamine; D014529:Uridine