Sequence-specific recognition of the major groove of RNA by deoxystreptamine

Biochemistry. 2002 May 21;41(20):6263-70. doi: 10.1021/bi0121609.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anti-Bacterial Agents / chemistry*
  • Base Sequence*
  • Binding Sites
  • Gentamicins / chemistry
  • Guanine / chemistry
  • Hexosamines / chemistry*
  • Hydrogen Bonding
  • Molecular Sequence Data
  • Nuclear Magnetic Resonance, Biomolecular
  • Paromomycin / chemistry
  • RNA, Ribosomal, 16S / chemistry*
  • Uridine / chemistry

Substances

  • Anti-Bacterial Agents
  • Gentamicins
  • Hexosamines
  • RNA, Ribosomal, 16S
  • gentamicin C
  • Guanine
  • Paromomycin
  • 2-deoxystreptamine
  • Uridine