Crystal structure of a bioactive pactamycin analog bound to the 30S ribosomal subunit

J Mol Biol. 2013 Oct 23;425(20):3907-10. doi: 10.1016/j.jmb.2013.05.004. Epub 2013 May 20.

Abstract

Biosynthetically and chemically derived analogs of the antibiotic pactamycin and de-6-methylsalicylyl (MSA)-pactamycin have attracted recent interest as potential antiprotozoal and antitumor drugs. Here, we report a 3.1-Å crystal structure of de-6-MSA-pactamycin bound to its target site on the Thermus thermophilus 30S ribosomal subunit. Although de-6-MSA-pactamycin lacks the MSA moiety, it shares the same binding site as pactamycin and induces a displacement of nucleic acid template bound at the E-site of the 30S. The structure highlights unique interactions between this pactamycin analog and the ribosome, which paves the way for therapeutic development of related compounds.

Keywords: E-site; MSA; antibiotic; mRNA; methylsalicylyl; translation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibiotics, Antineoplastic / chemistry
  • Antibiotics, Antineoplastic / metabolism
  • Crystallography, X-Ray
  • Models, Molecular
  • Molecular Conformation
  • Pactamycin / analogs & derivatives
  • Pactamycin / chemistry*
  • Pactamycin / metabolism*
  • Protein Binding
  • RNA, Ribosomal, 16S / chemistry
  • RNA, Ribosomal, 16S / metabolism
  • Ribosome Subunits, Small, Bacterial / chemistry*
  • Ribosome Subunits, Small, Bacterial / metabolism*
  • Thermus thermophilus / metabolism

Substances

  • Antibiotics, Antineoplastic
  • RNA, Ribosomal, 16S
  • Pactamycin