2pwt

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2pwt, resolution 1.800Å

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Crystal structure of the bacterial ribosomal decoding site complexed with aminoglycoside containing the L-HABA group

Overview

The crystal structure of the complex between oligonucleotide containing, the bacterial ribosomal decoding site (A site) and the synthetic, paromomycin analogue 1, which contains the, gamma-amino-alpha-hydroxybutyryl (L-haba) group at position N1 of ring II, (2-DOS ring), and an ether chain with an O-phenethylaminoethyl group at, position C2 of ring III, is reported. Interestingly, next to the, paromomycin analogue 1 specifically bound to the A site, a second molecule, of 1 with a different conformation is observed at the crystal packing, interface which mimics the A-minor interaction between two bulged-out, adenines from the A site and the codon-anticodon stem of the mRNA-tRNA, complex. Improved antibacterial activity supports the conclusion that, analogue 1 might affect protein synthesis on the ribosome in two different, ways: 1) specific binding to the A site forces maintenance of the "on", state with two bulged out adenines, and 2) a new binding mode of 1 to an, A-minor motif which stabilizes complex formation between the ribosome and, the mRNA-tRNA complex regardless of whether the codon-anticodon stem is of, the cognate or near-cognate type.

About this Structure

2PWT is a Protein complex structure of sequences from [1] with as ligand. Full crystallographic information is available from OCA.

Reference

Crystal Structure of the Bacterial Ribosomal Decoding Site Complexed with a Synthetic Doubly Functionalized Paromomycin Derivative: a New Specific Binding Mode to an A-Minor Motif Enhances in vitro Antibacterial Activity., Kondo J, Pachamuthu K, Francois B, Szychowski J, Hanessian S, Westhof E, ChemMedChem. 2007 Aug 27;. PMID:17722211

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