1l1h: Difference between revisions
New page: left|200px<br /><applet load="1l1h" size="450" color="white" frame="true" align="right" spinBox="true" caption="1l1h, resolution 1.75Å" /> '''Crystal Structure of... |
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[[Image:1l1h.gif|left|200px]]<br /><applet load="1l1h" size=" | [[Image:1l1h.gif|left|200px]]<br /><applet load="1l1h" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1l1h, resolution 1.75Å" /> | caption="1l1h, resolution 1.75Å" /> | ||
'''Crystal Structure of the Quadruplex DNA-Drug Complex'''<br /> | '''Crystal Structure of the Quadruplex DNA-Drug Complex'''<br /> | ||
==Overview== | ==Overview== | ||
Stabilisation of G-quadruplex structures formed from telomeric DNA, by | Stabilisation of G-quadruplex structures formed from telomeric DNA, by means of quadruplex-selective ligands, is a means of inhibiting the telomerase enzyme from catalysing the synthesis of telomeric DNA repeats. In order to understand the molecular basis of ligand-quadruplex recognition, the crystal structure has been determined of such a complex, at 1.75A resolution. This complex is between a dimeric antiparallel G-quadruplex formed from the Oxytricha nova telomeric DNA sequence d(GGGGTTTTGGGG), and a di-substituted aminoalkylamido acridine compound. The structure shows that the acridine moiety is bound at one end of the stack of G-quartets, within one of the thymine loops. It is held in place by a combination of stacking interactions and specific hydrogen bonds with thymine bases. The stability of the ligand in this binding site has been confirmed by a 2ns molecular dynamics simulation. | ||
==About this Structure== | ==About this Structure== | ||
1L1H is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with PYN and K as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | 1L1H is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with <scene name='pdbligand=PYN:'>PYN</scene> and <scene name='pdbligand=K:'>K</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1L1H OCA]. | ||
==Reference== | ==Reference== | ||
Structure of a G-quadruplex-ligand complex., Haider SM, Parkinson GN, Neidle S, J Mol Biol. 2003 Feb 7;326(1):117-25. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12547195 12547195] | Structure of a G-quadruplex-ligand complex., Haider SM, Parkinson GN, Neidle S, J Mol Biol. 2003 Feb 7;326(1):117-25. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12547195 12547195] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Haider, S | [[Category: Haider, S M.]] | ||
[[Category: Neidle, S.]] | [[Category: Neidle, S.]] | ||
[[Category: Parkinson, G | [[Category: Parkinson, G N.]] | ||
[[Category: K]] | [[Category: K]] | ||
[[Category: PYN]] | [[Category: PYN]] | ||
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[[Category: oxytricha]] | [[Category: oxytricha]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:40:22 2008'' | ||
Revision as of 11:40, 21 February 2008
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Crystal Structure of the Quadruplex DNA-Drug Complex
Overview
Stabilisation of G-quadruplex structures formed from telomeric DNA, by means of quadruplex-selective ligands, is a means of inhibiting the telomerase enzyme from catalysing the synthesis of telomeric DNA repeats. In order to understand the molecular basis of ligand-quadruplex recognition, the crystal structure has been determined of such a complex, at 1.75A resolution. This complex is between a dimeric antiparallel G-quadruplex formed from the Oxytricha nova telomeric DNA sequence d(GGGGTTTTGGGG), and a di-substituted aminoalkylamido acridine compound. The structure shows that the acridine moiety is bound at one end of the stack of G-quartets, within one of the thymine loops. It is held in place by a combination of stacking interactions and specific hydrogen bonds with thymine bases. The stability of the ligand in this binding site has been confirmed by a 2ns molecular dynamics simulation.
About this Structure
1L1H is a Protein complex structure of sequences from [1] with PYN and K as ligands. Full crystallographic information is available from OCA.
Reference
Structure of a G-quadruplex-ligand complex., Haider SM, Parkinson GN, Neidle S, J Mol Biol. 2003 Feb 7;326(1):117-25. PMID:12547195
Page seeded by OCA on Thu Feb 21 13:40:22 2008
