5DOY

Crystal structure of the Thermus thermophilus 70S ribosome in complex with antibiotic Hygromycin A, mRNA and three tRNAs in the A, P and E sites at 2.6A resolution

This is a non-PDB format compatible entry.

Replaces:  4Z3Q

Summary for 5DOY

• Entry DOI: 10.2210/pdb5doy/pdb
• Related: 4Z3S 5DOX
• Descriptor: 23S Ribosomal RNA, 50S Ribosomal Protein L14, 50S Ribosomal Protein L15, ... (62 entities in total)
• Functional Keywords: hygromycin a, a201a, antibiotic, 70s ribosome, inhibition of translation, peptidyl transferase inhibitors, trna accommodation intermediate, single-molecule fret, ribosome-antibiotic complex, ribosome/antibiotic
• Biological source: Escherichia coli; More
• Total number of polymer chains: 112
• Total formula weight: 4561674.42

Authors

Polikanov, Y.S.,Starosta, A.L.,Juette, M.F.,Altman, R.B.,Terry, D.S.,Lu, W.,Burnett, B.J.,Dinos, G.,Reynolds, K.,Blanchard, S.C.,Steitz, T.A.,Wilson, D.N. (deposition date: 2015-09-11, release date: 2015-12-30, Last modification date: 2025-03-19)

Primary citation

Polikanov, Y.S.,Starosta, A.L.,Juette, M.F.,Altman, R.B.,Terry, D.S.,Lu, W.,Burnett, B.J.,Dinos, G.,Reynolds, K.A.,Blanchard, S.C.,Steitz, T.A.,Wilson, D.N.
Distinct tRNA Accommodation Intermediates Observed on the Ribosome with the Antibiotics Hygromycin A and A201A.
Mol.Cell, 58:832-844, 2015

PubMed Abstract: The increase in multi-drug-resistant bacteria is limiting the effectiveness of currently approved antibiotics, leading to a renewed interest in antibiotics with distinct chemical scaffolds. We have solved the structures of the Thermus thermophilus 70S ribosome with A-, P-, and E-site tRNAs bound and in complex with either the aminocyclitol-containing antibiotic hygromycin A (HygA) or the nucleoside antibiotic A201A. Both antibiotics bind at the peptidyl transferase center and sterically occlude the CCA-end of the A-tRNA from entering the A site of the peptidyl transferase center. Single-molecule Förster resonance energy transfer (smFRET) experiments reveal that HygA and A201A specifically interfere with full accommodation of the A-tRNA, leading to the presence of tRNA accommodation intermediates and thereby inhibiting peptide bond formation. Thus, our results provide not only insight into the mechanism of action of HygA and A201A, but also into the fundamental process of tRNA accommodation during protein synthesis.

PubMed: 26028538
DOI: 10.1016/j.molcel.2015.04.014

Experimental method

X-RAY DIFFRACTION (2.6 Å)