2pwt: Difference between revisions

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==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.

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==

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==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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17722211 17722211]

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: Francois, B.]]

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[[Category: aminoglycoside; haba group; ribosomal decoding site; x-ray analysis; rna]]

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@@ Line 4: / Line 4: @@
 ==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.
+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==
@@ Line 10: / Line 10: @@
 ==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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17722211 17722211]
+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: Francois, B.]]
@@ Line 21: / Line 21: @@
 [[Category: aminoglycoside; haba group; ribosomal decoding site; x-ray analysis; rna]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 12:05:08 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:33:46 2008''