4B3R

Crystal structure of the 30S ribosome in complex with compound 30

Summary for 4B3R

• Entry DOI: 10.2210/pdb4b3r/pdb
• Related: 4B3M 4B3S 4B3T
• Descriptor: 16S RIBOSOMAL RNA, 30S RIBOSOMAL PROTEIN S10, 30S RIBOSOMAL PROTEIN S11, ... (28 entities in total)
• Functional Keywords: ribosome, aminoglycoside, antibiotic
• Biological source: THERMUS THERMOPHILUS HB8; More
• Total number of polymer chains: 23
• Total formula weight: 795360.17

Authors

Ng, C.L.,Lang, K.,Shcherbakov, D.,Matt, T.,Perez-Fernandez, D.,Patak, R.,Meyer, M.,Duscha, S.,Akbergenov, R.,Boukari, H.,Freihofer, P.,Kudyba, I.,Reddy, M.S.K.,Nandurikar, R.S.,Ramakrishnan, V.,Vasella, A.,Bottger, E.C. (deposition date: 2012-07-26, release date: 2013-08-07, Last modification date: 2024-10-09)

Primary citation

Perez-Fernandez, D.,Shcherbakov, D.,Matt, T.,Leong, N.C.,Kudyba, I.,Duscha, S.,Boukari, H.,Patak, R.,Dubakka, S.R.,Lang, K.,Meyer, M.,Akbergenov, R.,Freihofer, P.,Vaddi, S.,Thommes, P.,Ramakrishnan, V.,Vasella, A.,Bottger, E.C.
4'-O-Substitutions Determine Selectivity of Aminoglycoside Antibiotics
Nat.Commun., 5:3112-, 2014

PubMed Abstract: Clinical use of 2-deoxystreptamine aminoglycoside antibiotics, which target the bacterial ribosome, is compromised by adverse effects related to limited drug selectivity. Here we present a series of 4',6'-O-acetal and 4'-O-ether modifications on glucopyranosyl ring I of aminoglycosides. Chemical modifications were guided by measuring interactions between the compounds synthesized and ribosomes harbouring single point mutations in the drug-binding site, resulting in aminoglycosides that interact poorly with the drug-binding pocket of eukaryotic mitochondrial or cytosolic ribosomes. Yet, these compounds largely retain their inhibitory activity for bacterial ribosomes and show antibacterial activity. Our data indicate that 4'-O-substituted aminoglycosides possess increased selectivity towards bacterial ribosomes and little activity for any of the human drug-binding pockets.

PubMed: 24473108
DOI: 10.1038/NCOMMS4112

Experimental method

X-RAY DIFFRACTION (3 Å)