2pwt
From Proteopedia
(New page: 200px<br /><applet load="2pwt" size="350" color="white" frame="true" align="right" spinBox="true" caption="2pwt, resolution 1.800Å" /> '''Crystal structure o...) |
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==Overview== | ==Overview== | ||
| - | The crystal structure of the complex between oligonucleotide containing | + | 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== | ==About this Structure== | ||
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==Reference== | ==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 | + | 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 Nov 12;2(11):1631-1638. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17722211 17722211] |
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Francois, B.]] | [[Category: Francois, B.]] | ||
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[[Category: aminoglycoside; haba group; ribosomal decoding site; x-ray analysis; rna]] | [[Category: aminoglycoside; haba group; ribosomal decoding site; x-ray analysis; rna]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:33:46 2008'' |
Revision as of 16:33, 21 February 2008
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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 Nov 12;2(11):1631-1638. PMID:17722211
Page seeded by OCA on Thu Feb 21 18:33:46 2008
