4V9R

Crystal structure of antibiotic DITYROMYCIN bound to 70S ribosome

This is a non-PDB format compatible entry.

Summary for 4V9R

• Entry DOI: 10.2210/pdb4v9r/pdb
• Related PRD ID: PRD_001218
• Descriptor: 16S Ribosomal RNA, 30S Ribosomal Protein S10, 30S Ribosomal Protein S11, ... (61 entities in total)
• Functional Keywords: 70s, ribosome, dityromycin, ge82832, ribosomal protein s12, ef-g, translocation, dityromycin and ge82832 bind protein s12 and block ef-g catalyzed translocation, 30s subunit with bound mrna, p-site trna, ribosome-antibiotic complex, ribosome/antibiotic
• Biological source: Thermus thermophilus; More
• Total number of polymer chains: 110
• Total formula weight: 4455124.47

Authors

Bulkley, D.P.,Brandi, L.,Polikanov, Y.S.,Fabbretti, A.,O'Connor, M.,Gualerzi, C.O.,Steitz, T.A. (deposition date: 2013-12-05, release date: 2014-07-09, Last modification date: 2014-12-10)

Primary citation

Bulkley, D.,Brandi, L.,Polikanov, Y.S.,Fabbretti, A.,O'Connor, M.,Gualerzi, C.O.,Steitz, T.A.
The antibiotics dityromycin and GE82832 bind protein S12 and block EF-G-catalyzed translocation.
Cell Rep, 6:357-365, 2014

PubMed Abstract: The translocation of mRNA and tRNA through the ribosome is catalyzed by elongation factor G (EF-G), a universally conserved guanosine triphosphate hydrolase (GTPase). The mechanism by which the closely related decapeptide antibiotics dityromycin and GE82832 inhibit EF-G-catalyzed translocation is elucidated in this study. Using crystallographic and biochemical experiments, we demonstrate that these antibiotics bind to ribosomal protein S12 in solution alone as well as within the small ribosomal subunit, inducing long-range effects on the ribosomal head. The crystal structure of the antibiotic in complex with the 70S ribosome reveals that the binding involves conserved amino acid residues of S12 whose mutations result in in vitro and in vivo antibiotic resistance and loss of antibiotic binding. The data also suggest that GE82832/dityromycin inhibits EF-G-catalyzed translocation by disrupting a critical contact between EF-G and S12 that is required to stabilize the posttranslocational conformation of EF-G, thereby preventing the ribosome-EF-G complex from entering a conformation productive for translocation.

PubMed: 24412368
DOI: 10.1016/j.celrep.2013.12.024

Experimental method

X-RAY DIFFRACTION (3 Å)