1nzm - Revision history

OCA at 18:53, 29 November 2023

OCA — Wed, 29 Nov 2023 18:53:51 GMT

←Older revision		Revision as of 18:53, 29 November 2023
Line 1:		Line 1:

	==NMR structure of the parallel-stranded DNA quadruplex d(TTAGGGT)4 complexed with the telomerase inhibitor RHPS4==		==NMR structure of the parallel-stranded DNA quadruplex d(TTAGGGT)4 complexed with the telomerase inhibitor RHPS4==
-	<StructureSection load='1nzm' size='340' side='right'caption='[[1nzm~~]], [[NMR_Ensembles_of_Models \| 10 NMR models~~]]' scene=''>	+	<StructureSection load='1nzm' size='340' side='right'caption='[[1nzm]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1nzm]] is a 4 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NZM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1NZM FirstGlance]. <br>		<table><tr><td colspan='2'>[[1nzm]] is a 4 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NZM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1NZM FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=LG1:3,11-DIFLUORO-6,8,13-TRIMETHYL-8H-QUINO[4,3,2-KL]ACRIDIN-13-IUM'>LG1</scene~~></td></tr>~~	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1np9\|1np9]]</div~~></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=LG1:3,11-DIFLUORO-6,8,13-TRIMETHYL-8H-QUINO[4,3,2-KL]ACRIDIN-13-IUM'>LG1</scene></td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1nzm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nzm OCA], [https://pdbe.org/1nzm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1nzm RCSB], [https://www.ebi.ac.uk/pdbsum/1nzm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1nzm ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1nzm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nzm OCA], [https://pdbe.org/1nzm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1nzm RCSB], [https://www.ebi.ac.uk/pdbsum/1nzm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1nzm ProSAT]</span></td></tr>
	</table>		</table>
Line 22:		Line 22:
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Gavathiotis, E]]	+	[[Category: Gavathiotis E]]
-	[[Category: Heald~~, R A~~]]	+	[[Category: Heald RA]]
-	[[Category: Searle~~, M S~~]]	+	[[Category: Searle MS]]
-	[[Category: Stevens~~, M F.G]]~~	+	[[Category: Stevens MFG]]
-	~~[[Category: Dna]]~~	+
-	~~[[Category: Drug-dna interaction]]~~	+
-	~~[[Category: Molecular dynamic]]~~	+
-	~~[[Category: Nmr spectroscopy]]~~	+
-	~~[[Category: Quadruplex dna]]~~	+
-	~~[[Category: Telomerase inhibition]]~~	+
-	~~[[Category: Telomere]]~~	+
-	~~[[Category: Ttagggt repeat~~]]	+

OCA at 09:54, 12 May 2021

OCA — Wed, 12 May 2021 09:54:08 GMT

←Older revision		Revision as of 09:54, 12 May 2021
Line 3:		Line 3:
	<StructureSection load='1nzm' size='340' side='right'caption='[[1nzm]], [[NMR_Ensembles_of_Models \| 10 NMR models]]' scene=''>		<StructureSection load='1nzm' size='340' side='right'caption='[[1nzm]], [[NMR_Ensembles_of_Models \| 10 NMR models]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1nzm]] is a 4 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NZM OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=1NZM FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1nzm]] is a 4 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NZM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1NZM FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=LG1:3,11-DIFLUORO-6,8,13-TRIMETHYL-8H-QUINO[4,3,2-KL]ACRIDIN-13-IUM'>LG1</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=LG1:3,11-DIFLUORO-6,8,13-TRIMETHYL-8H-QUINO[4,3,2-KL]ACRIDIN-13-IUM'>LG1</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1np9\|1np9]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1np9\|1np9]]</div></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=1nzm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nzm OCA], [~~http~~://pdbe.org/1nzm PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=1nzm RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/1nzm PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=1nzm ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1nzm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nzm OCA], [https://pdbe.org/1nzm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1nzm RCSB], [https://www.ebi.ac.uk/pdbsum/1nzm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1nzm ProSAT]</span></td></tr>
	</table>		</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">

OCA at 07:18, 7 August 2019

OCA — Wed, 07 Aug 2019 07:18:48 GMT

←Older revision		Revision as of 07:18, 7 August 2019
Line 1:		Line 1:

	==NMR structure of the parallel-stranded DNA quadruplex d(TTAGGGT)4 complexed with the telomerase inhibitor RHPS4==		==NMR structure of the parallel-stranded DNA quadruplex d(TTAGGGT)4 complexed with the telomerase inhibitor RHPS4==
-	<StructureSection load='1nzm' size='340' side='right' caption='[[1nzm]], [[NMR_Ensembles_of_Models \| 10 NMR models]]' scene=''>	+	<StructureSection load='1nzm' size='340' side='right'caption='[[1nzm]], [[NMR_Ensembles_of_Models \| 10 NMR models]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1nzm]] is a 4 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NZM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1NZM FirstGlance]. <br>		<table><tr><td colspan='2'>[[1nzm]] is a 4 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NZM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1NZM FirstGlance]. <br>
Line 21:		Line 21:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Gavathiotis, E]]		[[Category: Gavathiotis, E]]
	[[Category: Heald, R A]]		[[Category: Heald, R A]]

OCA at 10:04, 1 November 2017

OCA — Wed, 01 Nov 2017 10:04:00 GMT

←Older revision		Revision as of 10:04, 1 November 2017
Line 1:		Line 1:
		+
	==NMR structure of the parallel-stranded DNA quadruplex d(TTAGGGT)4 complexed with the telomerase inhibitor RHPS4==		==NMR structure of the parallel-stranded DNA quadruplex d(TTAGGGT)4 complexed with the telomerase inhibitor RHPS4==
	<StructureSection load='1nzm' size='340' side='right' caption='[[1nzm]], [[NMR_Ensembles_of_Models \| 10 NMR models]]' scene=''>		<StructureSection load='1nzm' size='340' side='right' caption='[[1nzm]], [[NMR_Ensembles_of_Models \| 10 NMR models]]' scene=''>
Line 5:		Line 6:
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=LG1:3,11-DIFLUORO-6,8,13-TRIMETHYL-8H-QUINO[4,3,2-KL]ACRIDIN-13-IUM'>LG1</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=LG1:3,11-DIFLUORO-6,8,13-TRIMETHYL-8H-QUINO[4,3,2-KL]ACRIDIN-13-IUM'>LG1</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1np9\|1np9]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1np9\|1np9]]</td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1nzm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nzm OCA], [http://pdbe.org/1nzm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1nzm RCSB], [http://www.ebi.ac.uk/pdbsum/1nzm PDBsum]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1nzm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nzm OCA], [http://pdbe.org/1nzm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1nzm RCSB], [http://www.ebi.ac.uk/pdbsum/1nzm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1nzm ProSAT]</span></td></tr>
	</table>		</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">

OCA at 02:40, 12 September 2015

OCA — Sat, 12 Sep 2015 02:40:01 GMT

←Older revision		Revision as of 02:40, 12 September 2015
Line 5:		Line 5:
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=LG1:3,11-DIFLUORO-6,8,13-TRIMETHYL-8H-QUINO[4,3,2-KL]ACRIDIN-13-IUM'>LG1</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=LG1:3,11-DIFLUORO-6,8,13-TRIMETHYL-8H-QUINO[4,3,2-KL]ACRIDIN-13-IUM'>LG1</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1np9\|1np9]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1np9\|1np9]]</td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1nzm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nzm OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1nzm RCSB], [http://www.ebi.ac.uk/pdbsum/1nzm PDBsum]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1nzm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nzm OCA], [http://pdbe.org/1nzm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1nzm RCSB], [http://www.ebi.ac.uk/pdbsum/1nzm PDBsum]</span></td></tr>
	</table>		</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 15:		Line 15:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 1nzm" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 17:08, 5 January 2015

OCA — Mon, 05 Jan 2015 17:08:08 GMT

←Older revision		Revision as of 17:08, 5 January 2015
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1nzm]] is a 4 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NZM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1NZM FirstGlance]. <br>		<table><tr><td colspan='2'>[[1nzm]] is a 4 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NZM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1NZM FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=LG1:3,11-DIFLUORO-6,8,13-TRIMETHYL-8H-QUINO[4,3,2-KL]ACRIDIN-13-IUM'>LG1</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=LG1:3,11-DIFLUORO-6,8,13-TRIMETHYL-8H-QUINO[4,3,2-KL]ACRIDIN-13-IUM'>LG1</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1np9\|1np9]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1np9\|1np9]]</td></tr>
-	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1nzm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nzm OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1nzm RCSB], [http://www.ebi.ac.uk/pdbsum/1nzm PDBsum]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1nzm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nzm OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1nzm RCSB], [http://www.ebi.ac.uk/pdbsum/1nzm PDBsum]</span></td></tr>
-	<table>	+	</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 19:		Line 19:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Gavathiotis, E.]]	+	[[Category: Gavathiotis, E]]
-	[[Category: Heald, R A.]]	+	[[Category: Heald, R A]]
-	[[Category: Searle, M S.]]	+	[[Category: Searle, M S]]
-	[[Category: Stevens, M F.G.]]	+	[[Category: Stevens, M F.G]]
	[[Category: Dna]]		[[Category: Dna]]
	[[Category: Drug-dna interaction]]		[[Category: Drug-dna interaction]]

OCA at 18:41, 28 September 2014

OCA — Sun, 28 Sep 2014 18:41:05 GMT

←Older revision		Revision as of 18:41, 28 September 2014
Line 1:		Line 1:
-	[[~~Image:~~1nzm.~~png~~\|~~left~~\|~~200px~~]]	+	==NMR structure of the parallel-stranded DNA quadruplex d(TTAGGGT)4 complexed with the telomerase inhibitor RHPS4==
		+	<StructureSection load='1nzm' size='340' side='right' caption='[[1nzm]], [[NMR_Ensembles_of_Models \| 10 NMR models]]' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[1nzm]] is a 4 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NZM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1NZM FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=LG1:3,11-DIFLUORO-6,8,13-TRIMETHYL-8H-QUINO[4,3,2-KL]ACRIDIN-13-IUM'>LG1</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1np9\|1np9]]</td></tr>
		+	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1nzm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nzm OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1nzm RCSB], [http://www.ebi.ac.uk/pdbsum/1nzm PDBsum]</span></td></tr>
		+	<table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The NMR structure of the parallel-stranded DNA quadruplex d(TTAGGGT)(4), containing the human telomeric repeat, has been determined in solution in complex with a fluorinated pentacyclic quino[4,3,2-kl]acridinium cation (RHPS4). RHPS4 has been identified as a potent inhibitor of telomerase at submicromolar levels (IC(50) value of 0.33(+/-0.13)microM), exhibiting a wide differential between telomerase inhibition and acute cellular toxicity. All of the data point to RHPS4 exerting its chemotherapeutic potency through interaction with, and stabilisation of, four-stranded G-quadruplex structures. RHPS4 forms a dynamic interaction with d(TTAGGGT)(4), as evident from 1H and 19F linewidths, with fast exchange between binding sites induced at 318 K. Perturbations to DNA chemical shifts and 24 intermolecular nuclear Overhauser effects (NOEs) identify the 5'-ApG and 5'-GpT steps as the principle intercalation sites; a structural model has been refined using NOE-restrained molecular dynamics. The central G-tetrad core remains intact, with drug molecules stacking at the ends of the G-quadruplex. The partial positive charge on position 13-N of the acridine ring appears to act as a "pseudo" potassium ion and is positioned above the centre of the G-tetrad in the region of high negative charge density. In both ApG and GpT intercalation sites, the drug is seen to converge to the same orientation in which the pi-system of the drug overlaps primarily with two bases of each G-tetrad. The drug is held in place by stacking interactions with the G-tetrads; however, there is some evidence for a more dynamic, weakly stabilised A-tetrad that stacks partially on top of the drug at the 5'-end of the sequence. Together, the interactions of RHPS4 increase the t(m) of the quadruplex by approximately 20 degrees C. There is no evidence for drug intercalation within the G-quadruplex; however, the structural model strongly supports end-stacking interactions with the terminal G-tetrads.

-	~~{{STRUCTURE_1nzm\| PDB=1nzm \| SCENE= }}~~	+	Drug recognition and stabilisation of the parallel-stranded DNA quadruplex d(TTAGGGT)4 containing the human telomeric repeat.,Gavathiotis E, Heald RA, Stevens MF, Searle MS J Mol Biol. 2003 Nov 14;334(1):25-36. PMID:14596797<ref>PMID:14596797</ref>

-	~~===NMR structure~~ of the ~~parallel-stranded DNA quadruplex d(TTAGGGT)4 complexed with the telomerase inhibitor RHPS4===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~{{ABSTRACT_PUBMED_14596797}}~~	+	== References ==
-		+	<references/>
-	==~~About this Structure~~==	+	__TOC__
-	~~[[1nzm]] is a 4 chain structure. Full experimental information is available from [http:~~//~~oca.weizmann.ac.il/oca-bin/ocashort?id=1NZM OCA].~~	+	</StructureSection>
	[[Category: Gavathiotis, E.]]		[[Category: Gavathiotis, E.]]
	[[Category: Heald, R A.]]		[[Category: Heald, R A.]]

OCA: Protected "1nzm" [edit=sysop:move=sysop]

OCA — Wed, 05 Dec 2012 21:26:06 GMT

Protected "1nzm" [edit=sysop:move=sysop]

←Older revision

Revision as of 21:26, 5 December 2012

OCA at 21:26, 5 December 2012

OCA — Wed, 05 Dec 2012 21:26:01 GMT

←Older revision		Revision as of 21:26, 5 December 2012
Line 1:		Line 1:
-	{{Seed}}
	[[Image:1nzm.png\|left\|200px]]		[[Image:1nzm.png\|left\|200px]]

-	<!--
-	The line below this paragraph, containing "STRUCTURE_1nzm", creates the "Structure Box" on the page.
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	{{STRUCTURE_1nzm\| PDB=1nzm \| SCENE= }}		{{STRUCTURE_1nzm\| PDB=1nzm \| SCENE= }}

	===NMR structure of the parallel-stranded DNA quadruplex d(TTAGGGT)4 complexed with the telomerase inhibitor RHPS4===		===NMR structure of the parallel-stranded DNA quadruplex d(TTAGGGT)4 complexed with the telomerase inhibitor RHPS4===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_14596797}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 14596797 is the PubMed ID number.
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	{{ABSTRACT_PUBMED_14596797}}		{{ABSTRACT_PUBMED_14596797}}

	==About this Structure==		==About this Structure==
-	Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NZM OCA].	+	[[1nzm]] is a 4 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NZM OCA].
-		+
-	~~==Reference==~~	+
-	Drug recognition and stabilisation of the parallel-stranded DNA quadruplex d(TTAGGGT)4 containing the human telomeric repeat., Gavathiotis E, Heald RA, Stevens MF, Searle MS, J Mol Biol. 2003 Nov 14;334(1):25-36. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/14596797 14596797]	+
	[[Category: Gavathiotis, E.]]		[[Category: Gavathiotis, E.]]
	[[Category: Heald, R A.]]		[[Category: Heald, R A.]]
	[[Category: Searle, M S.]]		[[Category: Searle, M S.]]
	[[Category: Stevens, M F.G.]]		[[Category: Stevens, M F.G.]]
		+	[[Category: Dna]]
	[[Category: Drug-dna interaction]]		[[Category: Drug-dna interaction]]
	[[Category: Molecular dynamic]]		[[Category: Molecular dynamic]]
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	[[Category: Telomere]]		[[Category: Telomere]]
	[[Category: Ttagggt repeat]]		[[Category: Ttagggt repeat]]
-
-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 16:36:03 2008''

OCA at 13:36, 29 July 2008

OCA — Tue, 29 Jul 2008 13:36:08 GMT

←Older revision		Revision as of 13:36, 29 July 2008
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-	[[Image:1nzm.~~gif~~\|left\|200px]]	+	{{Seed}}
		+	[[Image:1nzm.png\|left\|200px]]

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	{{STRUCTURE_1nzm\| PDB=1nzm \| SCENE= }}		{{STRUCTURE_1nzm\| PDB=1nzm \| SCENE= }}

-	~~'''~~NMR structure of the parallel-stranded DNA quadruplex d(TTAGGGT)4 complexed with the telomerase inhibitor RHPS4~~'''~~	+	===NMR structure of the parallel-stranded DNA quadruplex d(TTAGGGT)4 complexed with the telomerase inhibitor RHPS4===


-	~~==Overview==~~	+	<!--
-	The ~~NMR structure of the parallel-stranded DNA quadruplex d(TTAGGGT)(4)~~, ~~containing~~ the ~~human telomeric repeat, has been determined in solution in complex with a fluorinated pentacyclic quino[4,3,2-kl]acridinium cation~~ (~~RHPS4). RHPS4 has been identified~~ as ~~a potent inhibitor of telomerase~~ at ~~submicromolar levels (IC(50) value of 0.33(+~~/-0.~~13)microM), exhibiting a wide differential between telomerase inhibition and acute cellular toxicity~~. All of the data point to RHPS4 exerting its chemotherapeutic potency through interaction with, and stabilisation of, four-stranded G-quadruplex structures. RHPS4 forms a dynamic interaction with d(TTAGGGT)(4), as evident from 1H and 19F linewidths, with fast exchange between binding sites induced at 318 K. Perturbations to DNA chemical shifts and 24 intermolecular nuclear Overhauser effects (NOEs) identify the 5'-ApG and 5'-GpT steps as the principle intercalation sites; a structural model has been refined using NOE-restrained molecular dynamics. The central G-tetrad core remains intact, with drug molecules stacking at the ends of the G-quadruplex. The partial positive charge on position 13-N of the acridine ring appears to act as a "pseudo" potassium ion and is ~~positioned above~~ the ~~centre of the G-tetrad in the region of high negative charge density~~. ~~In both ApG and GpT intercalation sites, the drug is seen to converge to the same orientation in which the pi~~-~~system of the drug overlaps primarily with two bases of each G~~-tetrad. The drug is held in place by stacking interactions with the G-tetrads; however, there is some evidence for a more dynamic, weakly stabilised A-tetrad that stacks partially on top of the drug at the 5'-end of the sequence. Together, the interactions of RHPS4 increase the t(m) of the quadruplex by approximately 20 degrees C. There is no evidence for drug intercalation within the G-quadruplex; however, the structural model strongly supports end-stacking interactions with the terminal G-tetrads.	+	The line below this paragraph, {{ABSTRACT_PUBMED_14596797}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 14596797 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_14596797}}

	==About this Structure==		==About this Structure==
-	Full ~~crystallographic~~ information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NZM OCA].	+	Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NZM OCA].

	==Reference==		==Reference==
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	[[Category: Telomere]]		[[Category: Telomere]]
	[[Category: Ttagggt repeat]]		[[Category: Ttagggt repeat]]
-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Sat May 3 03~~:10:57 2008''	+
		+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 16:36:03 2008''