385d - Revision history

OCA at 08:39, 7 February 2024

OCA — Wed, 07 Feb 2024 08:39:47 GMT

←Older revision		Revision as of 08:39, 7 February 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[385d]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=385D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=385D FirstGlance]. <br>		<table><tr><td colspan='2'>[[385d]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=385D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=385D FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NOD:N-ETHYLHYDROXY-DOXORUBICIN'>NOD</scene></td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.6Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NOD:N-ETHYLHYDROXY-DOXORUBICIN'>NOD</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=385d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=385d OCA], [https://pdbe.org/385d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=385d RCSB], [https://www.ebi.ac.uk/pdbsum/385d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=385d 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=385d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=385d OCA], [https://pdbe.org/385d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=385d RCSB], [https://www.ebi.ac.uk/pdbsum/385d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=385d ProSAT]</span></td></tr>
	</table>		</table>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	The cyanomorpholino analogue of antitumor anthracycline doxorubicin possesses an intense potency and differs from the parent compound in cross-resistance and other biological properties. The induction by cyanomorpholinodoxorubicin of both DNA cross-links and strand scission suggests an altered mode of action relative to doxorubicin with a different DNA-interacting capacity. We have co-crystallized 3'-(3-cyano-4-morpholinyl)-3'-desaminodoxorubicin (CMD) with the DNA hexamer d(CGATCG) and have determined the crystal structure at 0.16-nm resolution. The complex crystallizes in the space group P4(1)2(1)2 and is similar to the previously reported anthracycline/DNA structures, with the drug intercalated at the CpG step, forming hydrogen bonds with the guanine residue. The structure reveals that the morpholino moiety has undergone a major rearrangement with loss of the cyano group and opening of the morpholino ring. The compound actually bound to DNA in the complex resembles N-(2-hydroxyethyl)doxorubicin, which was previously identified as a hydrolysis product of CMD. No DNA alkylation has been observed. However, the structure shows that the active site of the morpholino ring, after dissociation of the cyano group, lies in the minor groove in proximity of the A/T base pair. This may indicate that a C/G base pair next to the intercalation site, with NH2 group in the minor groove, is required for DNA alkylation.
-
-	Degradation of the morpholino ring in the crystal structure of cyanomorpholinodoxorubicin complexed with d(CGATCG).,Ettorre A, Cirilli M, Ughetto G Eur J Biochem. 1998 Dec 1;258(2):350-4. PMID:9874199<ref>PMID:9874199</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 385d" style="background-color:#fffaf0;"></div>
-	== References ==
-	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Cirilli, M]]	+	[[Category: Cirilli M]]
-	[[Category: Ettorre, A]]	+	[[Category: Ettorre A]]
-	[[Category: Ughetto, G]]	+	[[Category: Ughetto G]]
-	~~[[Category: Complexed with drug]]~~	+
-	~~[[Category: Dna]]~~	+
-	~~[[Category: Double helix]]~~	+
-	~~[[Category: Right handed dna~~]]	+

OCA at 13:24, 4 May 2022

OCA — Wed, 04 May 2022 13:24:52 GMT

←Older revision		Revision as of 13:24, 4 May 2022
Line 3:		Line 3:
	<StructureSection load='385d' size='340' side='right'caption='[[385d]], [[Resolution\|resolution]] 1.60Å' scene=''>		<StructureSection load='385d' size='340' side='right'caption='[[385d]], [[Resolution\|resolution]] 1.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[385d]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=385D OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=385D FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[385d]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=385D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=385D FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NOD:N-ETHYLHYDROXY-DOXORUBICIN'>NOD</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NOD:N-ETHYLHYDROXY-DOXORUBICIN'>NOD</scene></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=385d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=385d OCA], [~~http~~://pdbe.org/385d PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=385d RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/385d PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=385d 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=385d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=385d OCA], [https://pdbe.org/385d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=385d RCSB], [https://www.ebi.ac.uk/pdbsum/385d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=385d ProSAT]</span></td></tr>
	</table>		</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">

OCA at 12:14, 29 July 2020

OCA — Wed, 29 Jul 2020 12:14:55 GMT

←Older revision		Revision as of 12:14, 29 July 2020
Line 1:		Line 1:

	==FORMATION OF A NEW COMPOUND IN THE CRYSTAL STRUCTURE OF CYANOMORPHOLINODOXORUBICIN COMPLEXED WITH D(CGATCG)==		==FORMATION OF A NEW COMPOUND IN THE CRYSTAL STRUCTURE OF CYANOMORPHOLINODOXORUBICIN COMPLEXED WITH D(CGATCG)==
-	<StructureSection load='385d' size='340' side='right' caption='[[385d]], [[Resolution\|resolution]] 1.60Å' scene=''>	+	<StructureSection load='385d' size='340' side='right'caption='[[385d]], [[Resolution\|resolution]] 1.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[385d]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=385D OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=385D FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[385d]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=385D OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=385D FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NOD:N-ETHYLHYDROXY-DOXORUBICIN'>NOD</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NOD:N-ETHYLHYDROXY-DOXORUBICIN'>NOD</scene></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=385d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=385d OCA], [http://pdbe.org/385d PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=385d RCSB], [http://www.ebi.ac.uk/pdbsum/385d PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=385d ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=385d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=385d OCA], [http://pdbe.org/385d PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=385d RCSB], [http://www.ebi.ac.uk/pdbsum/385d PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=385d ProSAT]</span></td></tr>
	</table>		</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 20:		Line 20:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Cirilli, M]]		[[Category: Cirilli, M]]
	[[Category: Ettorre, A]]		[[Category: Ettorre, A]]

OCA at 12:38, 11 August 2016

OCA — Thu, 11 Aug 2016 12:38:41 GMT

←Older revision		Revision as of 12:38, 11 August 2016
Line 1:		Line 1:
		+
	==FORMATION OF A NEW COMPOUND IN THE CRYSTAL STRUCTURE OF CYANOMORPHOLINODOXORUBICIN COMPLEXED WITH D(CGATCG)==		==FORMATION OF A NEW COMPOUND IN THE CRYSTAL STRUCTURE OF CYANOMORPHOLINODOXORUBICIN COMPLEXED WITH D(CGATCG)==
	<StructureSection load='385d' size='340' side='right' caption='[[385d]], [[Resolution\|resolution]] 1.60Å' scene=''>		<StructureSection load='385d' size='340' side='right' caption='[[385d]], [[Resolution\|resolution]] 1.60Å' scene=''>
Line 4:		Line 5:
	<table><tr><td colspan='2'>[[385d]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=385D OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=385D FirstGlance]. <br>		<table><tr><td colspan='2'>[[385d]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=385D OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=385D FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NOD:N-ETHYLHYDROXY-DOXORUBICIN'>NOD</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NOD:N-ETHYLHYDROXY-DOXORUBICIN'>NOD</scene></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=385d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=385d OCA], [http://www.rcsb.org/pdb/explore.do?structureId=385d RCSB], [http://www.ebi.ac.uk/pdbsum/385d 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=385d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=385d OCA], [http://pdbe.org/385d PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=385d RCSB], [http://www.ebi.ac.uk/pdbsum/385d PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=385d ProSAT]</span></td></tr>
	</table>		</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 14:		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 385d" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 10:19, 25 January 2015

OCA — Sun, 25 Jan 2015 10:19:53 GMT

←Older revision		Revision as of 10:19, 25 January 2015
Line 18:		Line 18:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Cirilli, M.]]	+	[[Category: Cirilli, M]]
-	[[Category: Ettorre, A.]]	+	[[Category: Ettorre, A]]
-	[[Category: Ughetto, G.]]	+	[[Category: Ughetto, G]]
	[[Category: Complexed with drug]]		[[Category: Complexed with drug]]
	[[Category: Dna]]		[[Category: Dna]]
	[[Category: Double helix]]		[[Category: Double helix]]
	[[Category: Right handed dna]]		[[Category: Right handed dna]]

OCA at 11:59, 29 October 2014

OCA — Wed, 29 Oct 2014 11:59:00 GMT

←Older revision		Revision as of 11:59, 29 October 2014
Line 1:		Line 1:
-	[[~~Image:~~385d.~~png~~\|~~left\|200px~~]]	+	==FORMATION OF A NEW COMPOUND IN THE CRYSTAL STRUCTURE OF CYANOMORPHOLINODOXORUBICIN COMPLEXED WITH D(CGATCG)==
		+	<StructureSection load='385d' size='340' side='right' caption='[[385d]], [[Resolution\|resolution]] 1.60Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[385d]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=385D OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=385D FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NOD:N-ETHYLHYDROXY-DOXORUBICIN'>NOD</scene></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=385d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=385d OCA], [http://www.rcsb.org/pdb/explore.do?structureId=385d RCSB], [http://www.ebi.ac.uk/pdbsum/385d PDBsum]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The cyanomorpholino analogue of antitumor anthracycline doxorubicin possesses an intense potency and differs from the parent compound in cross-resistance and other biological properties. The induction by cyanomorpholinodoxorubicin of both DNA cross-links and strand scission suggests an altered mode of action relative to doxorubicin with a different DNA-interacting capacity. We have co-crystallized 3'-(3-cyano-4-morpholinyl)-3'-desaminodoxorubicin (CMD) with the DNA hexamer d(CGATCG) and have determined the crystal structure at 0.16-nm resolution. The complex crystallizes in the space group P4(1)2(1)2 and is similar to the previously reported anthracycline/DNA structures, with the drug intercalated at the CpG step, forming hydrogen bonds with the guanine residue. The structure reveals that the morpholino moiety has undergone a major rearrangement with loss of the cyano group and opening of the morpholino ring. The compound actually bound to DNA in the complex resembles N-(2-hydroxyethyl)doxorubicin, which was previously identified as a hydrolysis product of CMD. No DNA alkylation has been observed. However, the structure shows that the active site of the morpholino ring, after dissociation of the cyano group, lies in the minor groove in proximity of the A/T base pair. This may indicate that a C/G base pair next to the intercalation site, with NH2 group in the minor groove, is required for DNA alkylation.

-	~~{{STRUCTURE_385d\| PDB=385d \| SCENE= }}~~	+	Degradation of the morpholino ring in the crystal structure of cyanomorpholinodoxorubicin complexed with d(CGATCG).,Ettorre A, Cirilli M, Ughetto G Eur J Biochem. 1998 Dec 1;258(2):350-4. PMID:9874199<ref>PMID:9874199</ref>

-	~~===FORMATION OF A NEW COMPOUND IN THE CRYSTAL STRUCTURE OF CYANOMORPHOLINODOXORUBICIN COMPLEXED WITH D(CGATCG)===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~{{ABSTRACT_PUBMED_9874199}}~~	+	== References ==
-		+	<references/>
-	==~~About this Structure~~==	+	__TOC__
-	~~[[385d]] is a 1 chain structure. Full crystallographic information is available from [http:~~//~~oca.weizmann.ac.il/oca-bin/ocashort?id=385D OCA].~~	+	</StructureSection>
	[[Category: Cirilli, M.]]		[[Category: Cirilli, M.]]
	[[Category: Ettorre, A.]]		[[Category: Ettorre, A.]]

OCA: Protected "385d" [edit=sysop:move=sysop]

OCA — Mon, 07 Jan 2013 22:01:39 GMT

Protected "385d" [edit=sysop:move=sysop]

←Older revision

Revision as of 22:01, 7 January 2013

OCA at 22:01, 7 January 2013

OCA — Mon, 07 Jan 2013 22:01:37 GMT

←Older revision		Revision as of 22:01, 7 January 2013
Line 1:		Line 1:
-	{{Seed}}
	[[Image:385d.png\|left\|200px]]		[[Image:385d.png\|left\|200px]]

-	<!--
-	The line below this paragraph, containing "STRUCTURE_385d", creates the "Structure Box" on the page.
-	You may change the PDB parameter (which sets the PDB file loaded into the applet)
-	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-	or leave the SCENE parameter empty for the default display.
-	-->
	{{STRUCTURE_385d\| PDB=385d \| SCENE= }}		{{STRUCTURE_385d\| PDB=385d \| SCENE= }}

	===FORMATION OF A NEW COMPOUND IN THE CRYSTAL STRUCTURE OF CYANOMORPHOLINODOXORUBICIN COMPLEXED WITH D(CGATCG)===		===FORMATION OF A NEW COMPOUND IN THE CRYSTAL STRUCTURE OF CYANOMORPHOLINODOXORUBICIN COMPLEXED WITH D(CGATCG)===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_9874199}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 9874199 is the PubMed ID number.
-	-->
	{{ABSTRACT_PUBMED_9874199}}		{{ABSTRACT_PUBMED_9874199}}

	==About this Structure==		==About this Structure==
-	Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=385D OCA].	+	[[385d]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=385D OCA].
-		+
-	~~==Reference==~~	+
-	Degradation of the morpholino ring in the crystal structure of cyanomorpholinodoxorubicin complexed with d(CGATCG)., Ettorre A, Cirilli M, Ughetto G, Eur J Biochem. 1998 Dec 1;258(2):350-4. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/9874199 9874199]	+
	[[Category: Cirilli, M.]]		[[Category: Cirilli, M.]]
	[[Category: Ettorre, A.]]		[[Category: Ettorre, A.]]
	[[Category: Ughetto, G.]]		[[Category: Ughetto, G.]]
	[[Category: Complexed with drug]]		[[Category: Complexed with drug]]
		+	[[Category: Dna]]
	[[Category: Double helix]]		[[Category: Double helix]]
	[[Category: Right handed dna]]		[[Category: Right handed dna]]
-
-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 08:38:25 2008''

OCA at 05:38, 29 July 2008

OCA — Tue, 29 Jul 2008 05:38:32 GMT

←Older revision		Revision as of 05:38, 29 July 2008
Line 1:		Line 1:
-	[[Image:385d.~~jpg~~\|left\|200px]]	+	{{Seed}}
		+	[[Image:385d.png\|left\|200px]]

	<!--		<!--
Line 9:		Line 10:
	{{STRUCTURE_385d\| PDB=385d \| SCENE= }}		{{STRUCTURE_385d\| PDB=385d \| SCENE= }}

-	~~'''~~FORMATION OF A NEW COMPOUND IN THE CRYSTAL STRUCTURE OF CYANOMORPHOLINODOXORUBICIN COMPLEXED WITH D(CGATCG)~~'''~~	+	===FORMATION OF A NEW COMPOUND IN THE CRYSTAL STRUCTURE OF CYANOMORPHOLINODOXORUBICIN COMPLEXED WITH D(CGATCG)===


-	~~==Overview==~~	+	<!--
-	The ~~cyanomorpholino analogue of antitumor anthracycline doxorubicin possesses an intense potency and differs from~~ the ~~parent compound in cross-resistance and other biological properties. The induction by cyanomorpholinodoxorubicin of both DNA cross-links and strand scission suggests an altered mode of action relative~~ to ~~doxorubicin with a different DNA-interacting capacity. We have co-crystallized 3'-(3-cyano-4-morpholinyl)-3'-desaminodoxorubicin (CMD) with~~ the ~~DNA hexamer d~~(~~CGATCG) and have determined the crystal structure~~ at 0.~~16-nm resolution~~. ~~The complex crystallizes in the space group P4(1~~)~~2(1)2 and~~ is ~~similar to~~ the ~~previously reported anthracycline/DNA structures, with the drug intercalated at the CpG step, forming hydrogen bonds with the guanine residue~~. The structure reveals that the morpholino moiety has undergone a major rearrangement with loss of the cyano group and opening of the morpholino ring. The compound actually bound to DNA in the complex resembles N-(2-hydroxyethyl)doxorubicin, which was previously identified as a hydrolysis product of CMD. No DNA alkylation has been observed. However, the structure shows that the active site of the morpholino ring, after dissociation of the cyano group, lies in the minor groove in proximity of the A/T base pair. This may indicate that a C/G base pair next to the intercalation site, with NH2 group in the minor groove, is required for DNA alkylation.	+	The line below this paragraph, {{ABSTRACT_PUBMED_9874199}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 9874199 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_9874199}}

	==About this Structure==		==About this Structure==
Line 26:		Line 30:
	[[Category: Double helix]]		[[Category: Double helix]]
	[[Category: Right handed dna]]		[[Category: Right handed dna]]
-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Sun May 4 20~~:18:16 2008''	+
		+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 08:38:25 2008''

OCA at 17:18, 4 May 2008

OCA — Sun, 04 May 2008 17:18:17 GMT

←Older revision		Revision as of 17:18, 4 May 2008
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	[[Image:385d.jpg\|left\|200px]]		[[Image:385d.jpg\|left\|200px]]

-	{{Structure	+	<!--
-	\|PDB~~= 385d \|SIZE=350\|CAPTION= <~~scene ~~name='initialview01'>385d</scene>~~, ~~resolution 1~~.~~600Å~~	+	The line below this paragraph, containing "STRUCTURE_385d", creates the "Structure Box" on the page.
-	~~\|SITE=~~	+	You may change the PDB parameter (which sets the PDB file loaded into the applet)
-	~~\|LIGAND= <scene name='pdbligand=DA:2'~~-~~DEOXYADENOSINE~~-5'-MONOPHOSPHATE'>DA</scene>, <scene name='pdbligand=DC:2'-DEOXYCYTIDINE-5'-MONOPHOSPHATE'>DC</scene>, <scene name='pdbligand=DG:2'-DEOXYGUANOSINE-5'-MONOPHOSPHATE'>DG</scene>, <scene name='pdbligand=DT:THYMIDINE-5'-MONOPHOSPHATE'>DT</scene>, <scene name='pdbligand=NOD:N-ETHYLHYDROXY-DOXORUBICIN'>NOD</scene>	+	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-	\|~~ACTIVITY~~=	+	or leave the SCENE parameter empty for the default display.
-	\|~~GENE~~=	+	-->
-	~~\|DOMAIN=~~	+	{{STRUCTURE_385d\| PDB=385d \| SCENE= }}
-	~~\|RELATEDENTRY=~~	+
-	\|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=385d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=385d OCA], [http://www.ebi.ac.uk/pdbsum/385d PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=385d RCSB]</span>	+
-	}}	+

	'''FORMATION OF A NEW COMPOUND IN THE CRYSTAL STRUCTURE OF CYANOMORPHOLINODOXORUBICIN COMPLEXED WITH D(CGATCG)'''		'''FORMATION OF A NEW COMPOUND IN THE CRYSTAL STRUCTURE OF CYANOMORPHOLINODOXORUBICIN COMPLEXED WITH D(CGATCG)'''
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	==About this Structure==		==About this Structure==
-	~~385D is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/ ].~~ Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=385D OCA].	+	Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=385D OCA].

	==Reference==		==Reference==
	Degradation of the morpholino ring in the crystal structure of cyanomorpholinodoxorubicin complexed with d(CGATCG)., Ettorre A, Cirilli M, Ughetto G, Eur J Biochem. 1998 Dec 1;258(2):350-4. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/9874199 9874199]		Degradation of the morpholino ring in the crystal structure of cyanomorpholinodoxorubicin complexed with d(CGATCG)., Ettorre A, Cirilli M, Ughetto G, Eur J Biochem. 1998 Dec 1;258(2):350-4. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/9874199 9874199]
-	[[Category: Protein complex]]
	[[Category: Cirilli, M.]]		[[Category: Cirilli, M.]]
	[[Category: Ettorre, A.]]		[[Category: Ettorre, A.]]
	[[Category: Ughetto, G.]]		[[Category: Ughetto, G.]]
-	[[Category: ~~complexed~~ with drug]]	+	[[Category: Complexed with drug]]
-	[[Category: ~~double~~ helix]]	+	[[Category: Double helix]]
-	[[Category: ~~right~~ handed dna]]	+	[[Category: Right handed dna]]
-		+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 20:18:16 2008''
-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Mon Mar 31 05~~:22:05 2008''	+