2bq2
From Proteopedia
(New page: 200px<br /><applet load="2bq2" size="350" color="white" frame="true" align="right" spinBox="true" caption="2bq2" /> '''SOLUTION STRUCTURE OF THE DNA DUPLEX ACGCGU-...) |
|||
| Line 4: | Line 4: | ||
==Overview== | ==Overview== | ||
| - | Quinolones are antibacterial drugs that are thought to bind preferentially | + | Quinolones are antibacterial drugs that are thought to bind preferentially to disturbed regions of DNA. They do not fall into the classical categories of intercalators, groove binders or electrostatic binders to the backbone. We solved the 3D structure of the DNA duplex (ACGCGU-NA)2, where NA denotes a nalidixic acid residue covalently linked to the 2'-position of 2'-amino-2'-deoxyuridine, by NMR and restrained torsion angle molecular dynamics (MD). In the complex, the quinolones stack on G:C base pairs of the core tetramer and disrupt the terminal A:U base pair. The displaced dA residues can stack on the quinolones, while the uracil rings bind in the minor groove. The duplex-bridging interactions of the drugs and the contacts of the displaced nucleotides explain the high UV-melting temperature for d(ACGCGU-NA)2 of up to 53 degrees C. Further, non-covalently linked complexes between quinolones and DNA of the sequence ACGCGT can be generated via MD using constraints obtained for d(ACGCGU-NA)2. This is demonstrated for unconjugated nalidixic acid and its 6-fluoro derivative. The well-ordered and tightly packed structures thus obtained are compatible with a published model for the quinolone-DNA complex in the active site of gyrases. |
==About this Structure== | ==About this Structure== | ||
| Line 25: | Line 25: | ||
[[Category: synthetic hybrid]] | [[Category: synthetic hybrid]] | ||
| - | ''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 16:40:26 2008'' |
Revision as of 14:40, 21 February 2008
|
SOLUTION STRUCTURE OF THE DNA DUPLEX ACGCGU-NA WITH A 2' AMIDO-LINKED NALIDIXIC ACID RESIDUE AT THE 3' TERMINAL NUCLEOTIDE
Overview
Quinolones are antibacterial drugs that are thought to bind preferentially to disturbed regions of DNA. They do not fall into the classical categories of intercalators, groove binders or electrostatic binders to the backbone. We solved the 3D structure of the DNA duplex (ACGCGU-NA)2, where NA denotes a nalidixic acid residue covalently linked to the 2'-position of 2'-amino-2'-deoxyuridine, by NMR and restrained torsion angle molecular dynamics (MD). In the complex, the quinolones stack on G:C base pairs of the core tetramer and disrupt the terminal A:U base pair. The displaced dA residues can stack on the quinolones, while the uracil rings bind in the minor groove. The duplex-bridging interactions of the drugs and the contacts of the displaced nucleotides explain the high UV-melting temperature for d(ACGCGU-NA)2 of up to 53 degrees C. Further, non-covalently linked complexes between quinolones and DNA of the sequence ACGCGT can be generated via MD using constraints obtained for d(ACGCGU-NA)2. This is demonstrated for unconjugated nalidixic acid and its 6-fluoro derivative. The well-ordered and tightly packed structures thus obtained are compatible with a published model for the quinolone-DNA complex in the active site of gyrases.
About this Structure
2BQ2 is a Single protein structure of sequence from [1] with as ligand. Full crystallographic information is available from OCA.
Reference
Molecular details of quinolone-DNA interactions: solution structure of an unusually stable DNA duplex with covalently linked nalidixic acid residues and non-covalent complexes derived from it., Siegmund K, Maheshwary S, Narayanan S, Connors W, Riedrich M, Printz M, Richert C, Nucleic Acids Res. 2005 Aug 26;33(15):4838-48. Print 2005. PMID:16126848
Page seeded by OCA on Thu Feb 21 16:40:26 2008
