Frank Murphy

Publications (3)12.49 Total impact

• Article: A structural basis for streptomycin-induced misreading of the genetic code.

  Hasan Demirci, Frank Murphy, Eileen Murphy, Steven T Gregory, Albert E Dahlberg, Gerwald Jogl
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  ABSTRACT: During protein synthesis, the ribosome selects aminoacyl-transfer RNAs with anticodons matching the messenger RNA codon present in the A site of the small ribosomal subunit. The aminoglycoside antibiotic streptomycin disrupts decoding by binding close to the site of codon recognition. Here we use X-ray crystallography to define the impact of streptomycin on the decoding site of the Thermus thermophilus 30S ribosomal subunit in complexes with cognate or near-cognate anticodon stem-loop analogues and messenger RNA. Our crystal structures display a significant local distortion of 16S ribosomal RNA induced by streptomycin, including the crucial bases A1492 and A1493 that participate directly in codon recognition. Consistent with kinetic data, we observe that streptomycin stabilizes the near-cognate anticodon stem-loop analogue complex, while destabilizing the cognate anticodon stem-loop analogue complex. These data reveal how streptomycin disrupts the recognition of cognate anticodon stem-loop analogues and yet improves recognition of a near-cognate anticodon stem-loop analogue.
  Nature Communications 01/2013; 4:1355. · 7.40 Impact Factor
• Chapter: Genetic and crystallographic approaches to investigating ribosome structure and function

  Steven T. Gregory, Hasan Demirci, Jennifer F. Carr, Riccardo Belardinelli, Jill R. Thompson, Dale Cameron, Daniel Rodriguez-Correa, Frank Murphy, Gerwald Jogl, Albert E. Dahlberg
  07/2011: pages 57-64; , ISBN: 978-3-7091-0214-5
• Article: Modification of 16S ribosomal RNA by the KsgA methyltransferase restructures the 30S subunit to optimize ribosome function.

  Hasan Demirci, Frank Murphy, Riccardo Belardinelli, Ann C Kelley, V Ramakrishnan, Steven T Gregory, Albert E Dahlberg, Gerwald Jogl
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  ABSTRACT: All organisms incorporate post-transcriptional modifications into ribosomal RNA, influencing ribosome assembly and function in ways that are poorly understood. The most highly conserved modification is the dimethylation of two adenosines near the 3' end of the small subunit rRNA. Lack of these methylations due to deficiency in the KsgA methyltransferase stimulates translational errors during both the initiation and elongation phases of protein synthesis and confers resistance to the antibiotic kasugamycin. Here, we present the X-ray crystal structure of the Thermus thermophilus 30S ribosomal subunit lacking these dimethylations. Our data indicate that the KsgA-directed methylations facilitate structural rearrangements in order to establish a functionally optimum subunit conformation during the final stages of ribosome assembly.
  RNA 10/2010; 16(12):2319-24. · 5.09 Impact Factor