1ly3 - Revision history

OCA at 07:37, 14 February 2024

OCA — Wed, 14 Feb 2024 07:37:17 GMT

←Older revision		Revision as of 07:37, 14 February 2024
Line 3:		Line 3:
	<StructureSection load='1ly3' size='340' side='right'caption='[[1ly3]], [[Resolution\|resolution]] 1.90Å' scene=''>		<StructureSection load='1ly3' size='340' side='right'caption='[[1ly3]], [[Resolution\|resolution]] 1.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1ly3]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Pneca Pneca~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LY3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1LY3 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1ly3]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Pneumocystis_carinii Pneumocystis carinii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LY3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1LY3 FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=COG:2~~,~~4-DIAMINO-6-~~[~~N-(2,5-DIMETHOXYBENZYL)-N-METHYLAMINO~~]~~QUINAZOLINE'>COG</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</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]] 1.9Å</td></tr>
-	<tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat"><~~div style~~='~~overflow~~: ~~auto; max~~-~~height: 3em;'>~~[~~[1ly4\|1ly4~~]~~]</div~~></td><~~/tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=COG:2,4-DIAMINO-6-[N-(2,5-DIMETHOXYBENZYL)-N-METHYLAMINO]QUINAZOLINE'>COG</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr>
-	~~<tr id~~='~~activity'><td class~~=~~"sblockLbl"><b>Activity~~:~~</b></td><td class="sblockDat"><span class='plainlinks~~'>~~[https://en.wikipedia.org/wiki/Dihydrofolate_reductase Dihydrofolate reductase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.3 1.5.1.3]~~ </~~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=1ly3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ly3 OCA], [https://pdbe.org/1ly3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ly3 RCSB], [https://www.ebi.ac.uk/pdbsum/1ly3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ly3 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=1ly3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ly3 OCA], [https://pdbe.org/1ly3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ly3 RCSB], [https://www.ebi.ac.uk/pdbsum/1ly3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ly3 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/DYR_PNECA DYR_PNECA]] Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis.	+	[https://www.uniprot.org/uniprot/DYR_PNECA DYR_PNECA] Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis.
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
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	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1ly3 ConSurf].		</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1ly3 ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	Structural studies of two ternary complexes of Pneumocystis carinii dihydrofolate reductase (pcDHFR) with the cofactor NADP(+) and potent antifolates, the N9-C10 reversed-bridge inhibitor 2,4-diamino-6-[N-(2',5'-dimethoxybenzyl)-N-methylamino]quinazoline (1) and its 3',5'-dimethoxypyrido[2,3-d]pyrimidine analog (2), were carried out. Data for the monoclinic crystals were refined to 1.90 A resolution for the complex with (1) (R = 0.178) and to 2.1 A resolution for the complex with (2) (R = 0.193). The effect of the N9-C10 reversed-bridge geometry is to distort the bridge from coplanarity with the pyrido[2,3-d]pyrimidine or quinazoline ring system and to twist the C10 methylene conformation toward a gauche conformation. This change also influences the conformation of the methoxybenzyl ring, moving it away from a trans position. This change places the 5'-methoxy group deeper within the hydrophobic pocket made by Ile65, Pro66 and Phe69 of the pcDHFR active site. These results also revealed the first observation of an unusual conformation for the reversed-bridge geometry (C5-C6-N9-C10 torsion angle) in antifolate (2). The electron density is consistent with the presence of two models (conformers 2-1 and 2-2) that result from inversion of the geometry at N9. The four examples of N9-C10 reversed-bridge antifolates cluster in two conformations, with the structure of quinazoline (1) similar to that previously reported for its 2',5'-dimethoxypyrido[2,3-d]pyrimidine analog (3). The two conformers of (2) differ from these and each other by a twisted-bridge geometry that results in the dimethoxybenzyl ring occupying the same conformational space. Conformer 2-2 also has the N9-C10 reversed bridge perpendicular to the pyrido[2,3-d]pyrimidine plane, in contrast to the gauche-trans conformation normally observed. As a result of these changes, the N9 methyl probes conformational space in the active site not normally occupied by antifolate structures. The N9 methyl of conformer 2-2 makes close contacts to the conserved Leu25 as well as the hydroxyl O atoms of the nicotinamide ribose and Ser64, whereas the other three reversed-bridge conformers make weak hydrophobic contacts with Ile123, Thr61 and Ile65. These antifolates are ten times more selective for pcDHFR than the C9-N10 bridge parent trimetrexate. However, pyrido[2,3-d]pyrimidines (2) and (3) are three times more selective for pcDHFR than quinazoline (1) is for rat liver DHFR. These data suggest that the loss of hydrogen-bonding interactions with N8 is more important to potency than the interactions of the methoxybenzyl substituents.
-
-	Analysis of quinazoline and pyrido[2,3-d]pyrimidine N9-C10 reversed-bridge antifolates in complex with NADP+ and Pneumocystis carinii dihydrofolate reductase.,Cody V, Galitsky N, Luft JR, Pangborn W, Queener SF, Gangjee A Acta Crystallogr D Biol Crystallogr. 2002 Sep;58(Pt 9):1393-9. Epub 2002, Aug 23. PMID:12198294<ref>PMID:12198294</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 1ly3" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
	*[[Dihydrofolate reductase 3D structures\|Dihydrofolate reductase 3D structures]]		*[[Dihydrofolate reductase 3D structures\|Dihydrofolate reductase 3D structures]]
-	== References ==
-	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Dihydrofolate reductase]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Pneca~~]]	+	[[Category: Pneumocystis carinii]]
-	[[Category: Cody, V]]	+	[[Category: Cody V]]
-	[[Category: Galitsky, N]]	+	[[Category: Galitsky N]]
-	[[Category: Gangjee, A]]	+	[[Category: Gangjee A]]
-	[[Category: Luft~~, J R~~]]	+	[[Category: Luft JR]]
-	[[Category: Pangborn, W]]	+	[[Category: Pangborn W]]
-	[[Category: Queener~~, S F]]~~	+	[[Category: Queener SF]]
-	~~[[Category: Oxidoreductase]]~~	+
-	~~[[Category: Pcdhfr reversed bridge antifolate~~]]	+

OCA at 06:50, 18 August 2021

OCA — Wed, 18 Aug 2021 06:50:38 GMT

←Older revision		Revision as of 06:50, 18 August 2021
Line 3:		Line 3:
	<StructureSection load='1ly3' size='340' side='right'caption='[[1ly3]], [[Resolution\|resolution]] 1.90Å' scene=''>		<StructureSection load='1ly3' size='340' side='right'caption='[[1ly3]], [[Resolution\|resolution]] 1.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1ly3]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Pneca Pneca]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LY3 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=1LY3 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1ly3]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Pneca Pneca]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LY3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1LY3 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=COG:2,4-DIAMINO-6-[N-(2,5-DIMETHOXYBENZYL)-N-METHYLAMINO]QUINAZOLINE'>COG</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=COG:2,4-DIAMINO-6-[N-(2,5-DIMETHOXYBENZYL)-N-METHYLAMINO]QUINAZOLINE'>COG</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1ly4\|1ly4]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1ly4\|1ly4]]</div></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://en.wikipedia.org/wiki/Dihydrofolate_reductase Dihydrofolate reductase], with EC number [~~http~~://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.3 1.5.1.3] </span></td></tr>	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Dihydrofolate_reductase Dihydrofolate reductase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.3 1.5.1.3] </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=1ly3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ly3 OCA], [~~http~~://pdbe.org/1ly3 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=1ly3 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/1ly3 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=1ly3 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=1ly3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ly3 OCA], [https://pdbe.org/1ly3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ly3 RCSB], [https://www.ebi.ac.uk/pdbsum/1ly3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ly3 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/DYR_PNECA DYR_PNECA]] Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis.	+	[[https://www.uniprot.org/uniprot/DYR_PNECA DYR_PNECA]] Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis.
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]

OCA at 12:31, 13 November 2019

OCA — Wed, 13 Nov 2019 12:31:17 GMT

←Older revision		Revision as of 12:31, 13 November 2019
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	==ANALYSIS OF QUINAZOLINE AND PYRIDOPYRIMIDINE N9-C10 REVERSED BRIDGE ANTIFOLATES IN COMPLEX WITH NADP+ AND PNEUMOCYSTIS CARINII DIHYDROFOLATE REDUCTASE==		==ANALYSIS OF QUINAZOLINE AND PYRIDOPYRIMIDINE N9-C10 REVERSED BRIDGE ANTIFOLATES IN COMPLEX WITH NADP+ AND PNEUMOCYSTIS CARINII DIHYDROFOLATE REDUCTASE==
-	<StructureSection load='1ly3' size='340' side='right' caption='[[1ly3]], [[Resolution\|resolution]] 1.90Å' scene=''>	+	<StructureSection load='1ly3' size='340' side='right'caption='[[1ly3]], [[Resolution\|resolution]] 1.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1ly3]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Pneca Pneca]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LY3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1LY3 FirstGlance]. <br>		<table><tr><td colspan='2'>[[1ly3]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Pneca Pneca]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LY3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1LY3 FirstGlance]. <br>
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	</div>		</div>
	<div class="pdbe-citations 1ly3" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 1ly3" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Dihydrofolate reductase 3D structures\|Dihydrofolate reductase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 35:		Line 38:
	</StructureSection>		</StructureSection>
	[[Category: Dihydrofolate reductase]]		[[Category: Dihydrofolate reductase]]
		+	[[Category: Large Structures]]
	[[Category: Pneca]]		[[Category: Pneca]]
	[[Category: Cody, V]]		[[Category: Cody, V]]

OCA at 08:06, 31 January 2018

OCA — Wed, 31 Jan 2018 08:06:26 GMT

←Older revision		Revision as of 08:06, 31 January 2018
Line 1:		Line 1:
		+
	==ANALYSIS OF QUINAZOLINE AND PYRIDOPYRIMIDINE N9-C10 REVERSED BRIDGE ANTIFOLATES IN COMPLEX WITH NADP+ AND PNEUMOCYSTIS CARINII DIHYDROFOLATE REDUCTASE==		==ANALYSIS OF QUINAZOLINE AND PYRIDOPYRIMIDINE N9-C10 REVERSED BRIDGE ANTIFOLATES IN COMPLEX WITH NADP+ AND PNEUMOCYSTIS CARINII DIHYDROFOLATE REDUCTASE==
	<StructureSection load='1ly3' size='340' side='right' caption='[[1ly3]], [[Resolution\|resolution]] 1.90Å' scene=''>		<StructureSection load='1ly3' size='340' side='right' caption='[[1ly3]], [[Resolution\|resolution]] 1.90Å' scene=''>
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	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1ly4\|1ly4]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1ly4\|1ly4]]</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dihydrofolate_reductase Dihydrofolate reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.3 1.5.1.3] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dihydrofolate_reductase Dihydrofolate reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.3 1.5.1.3] </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=1ly3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ly3 OCA], [http://pdbe.org/1ly3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1ly3 RCSB], [http://www.ebi.ac.uk/pdbsum/1ly3 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=1ly3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ly3 OCA], [http://pdbe.org/1ly3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1ly3 RCSB], [http://www.ebi.ac.uk/pdbsum/1ly3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1ly3 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 14:		Line 15:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ly/1ly3_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ly/1ly3_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
Line 29:		Line 30:
	</div>		</div>
	<div class="pdbe-citations 1ly3" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 1ly3" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[Dihydrofolate reductase\|Dihydrofolate reductase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 19:17, 9 February 2016

OCA — Tue, 09 Feb 2016 19:17:19 GMT

←Older revision		Revision as of 19:17, 9 February 2016
Line 18:		Line 18:
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</jmolCheckbox>
-	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/~~chain_selection~~.php?pdb_ID=~~2ata~~ ConSurf].	+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1ly3 ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">

OCA at 01:16, 11 September 2015

OCA — Fri, 11 Sep 2015 01:16:27 GMT

←Older revision		Revision as of 01:16, 11 September 2015
Line 2:		Line 2:
	<StructureSection load='1ly3' size='340' side='right' caption='[[1ly3]], [[Resolution\|resolution]] 1.90Å' scene=''>		<StructureSection load='1ly3' size='340' side='right' caption='[[1ly3]], [[Resolution\|resolution]] 1.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1ly3]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Pneumocystis_carinii Pneumocystis carinii~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LY3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1LY3 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1ly3]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Pneca Pneca]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LY3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1LY3 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=COG:2,4-DIAMINO-6-[N-(2,5-DIMETHOXYBENZYL)-N-METHYLAMINO]QUINAZOLINE'>COG</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=COG:2,4-DIAMINO-6-[N-(2,5-DIMETHOXYBENZYL)-N-METHYLAMINO]QUINAZOLINE'>COG</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1ly4\|1ly4]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1ly4\|1ly4]]</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dihydrofolate_reductase Dihydrofolate reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.3 1.5.1.3] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dihydrofolate_reductase Dihydrofolate reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.3 1.5.1.3] </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=1ly3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ly3 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1ly3 RCSB], [http://www.ebi.ac.uk/pdbsum/1ly3 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=1ly3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ly3 OCA], [http://pdbe.org/1ly3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1ly3 RCSB], [http://www.ebi.ac.uk/pdbsum/1ly3 PDBsum]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 28:		Line 28:
	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 1ly3" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 36:		Line 37:
	</StructureSection>		</StructureSection>
	[[Category: Dihydrofolate reductase]]		[[Category: Dihydrofolate reductase]]
-	[[Category: ~~Pneumocystis carinii~~]]	+	[[Category: Pneca]]
	[[Category: Cody, V]]		[[Category: Cody, V]]
	[[Category: Galitsky, N]]		[[Category: Galitsky, N]]

OCA at 08:58, 25 December 2014

OCA — Thu, 25 Dec 2014 08:58:05 GMT

←Older revision		Revision as of 08:58, 25 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1ly3]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Pneumocystis_carinii Pneumocystis carinii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LY3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1LY3 FirstGlance]. <br>		<table><tr><td colspan='2'>[[1ly3]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Pneumocystis_carinii Pneumocystis carinii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LY3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1LY3 FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=COG:2,4-DIAMINO-6-[N-(2,5-DIMETHOXYBENZYL)-N-METHYLAMINO]QUINAZOLINE'>COG</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=COG:2,4-DIAMINO-6-[N-(2,5-DIMETHOXYBENZYL)-N-METHYLAMINO]QUINAZOLINE'>COG</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1ly4\|1ly4]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1ly4\|1ly4]]</td></tr>
-	<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dihydrofolate_reductase Dihydrofolate reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.3 1.5.1.3] </span></td></tr>	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dihydrofolate_reductase Dihydrofolate reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.3 1.5.1.3] </span></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=1ly3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ly3 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1ly3 RCSB], [http://www.ebi.ac.uk/pdbsum/1ly3 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=1ly3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ly3 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1ly3 RCSB], [http://www.ebi.ac.uk/pdbsum/1ly3 PDBsum]</span></td></tr>
-	<table>	+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/DYR_PNECA DYR_PNECA]] Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis.
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 35:		Line 37:
	[[Category: Dihydrofolate reductase]]		[[Category: Dihydrofolate reductase]]
	[[Category: Pneumocystis carinii]]		[[Category: Pneumocystis carinii]]
-	[[Category: Cody, V.]]	+	[[Category: Cody, V]]
-	[[Category: Galitsky, N.]]	+	[[Category: Galitsky, N]]
-	[[Category: Gangjee, A.]]	+	[[Category: Gangjee, A]]
-	[[Category: Luft, J R.]]	+	[[Category: Luft, J R]]
-	[[Category: Pangborn, W.]]	+	[[Category: Pangborn, W]]
-	[[Category: Queener, S F.]]	+	[[Category: Queener, S F]]
	[[Category: Oxidoreductase]]		[[Category: Oxidoreductase]]
	[[Category: Pcdhfr reversed bridge antifolate]]		[[Category: Pcdhfr reversed bridge antifolate]]

OCA at 15:11, 28 September 2014

OCA — Sun, 28 Sep 2014 15:11:27 GMT

←Older revision		Revision as of 15:11, 28 September 2014
Line 1:		Line 1:
-	[[~~Image:~~1ly3.~~png~~\|~~left~~\|200px]]	+	==ANALYSIS OF QUINAZOLINE AND PYRIDOPYRIMIDINE N9-C10 REVERSED BRIDGE ANTIFOLATES IN COMPLEX WITH NADP+ AND PNEUMOCYSTIS CARINII DIHYDROFOLATE REDUCTASE==
		+	<StructureSection load='1ly3' size='340' side='right' caption='[[1ly3]], [[Resolution\|resolution]] 1.90Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[1ly3]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Pneumocystis_carinii Pneumocystis carinii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LY3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1LY3 FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=COG:2,4-DIAMINO-6-[N-(2,5-DIMETHOXYBENZYL)-N-METHYLAMINO]QUINAZOLINE'>COG</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1ly4\|1ly4]]</td></tr>
		+	<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dihydrofolate_reductase Dihydrofolate reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.3 1.5.1.3] </span></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=1ly3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ly3 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1ly3 RCSB], [http://www.ebi.ac.uk/pdbsum/1ly3 PDBsum]</span></td></tr>
		+	<table>
		+	== Evolutionary Conservation ==
		+	[[Image:Consurf_key_small.gif\|200px\|right]]
		+	Check<jmol>
		+	<jmolCheckbox>
		+	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ly/1ly3_consurf.spt"</scriptWhenChecked>
		+	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
		+	<text>to colour the structure by Evolutionary Conservation</text>
		+	</jmolCheckbox>
		+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
		+	<div style="clear:both"></div>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Structural studies of two ternary complexes of Pneumocystis carinii dihydrofolate reductase (pcDHFR) with the cofactor NADP(+) and potent antifolates, the N9-C10 reversed-bridge inhibitor 2,4-diamino-6-[N-(2',5'-dimethoxybenzyl)-N-methylamino]quinazoline (1) and its 3',5'-dimethoxypyrido[2,3-d]pyrimidine analog (2), were carried out. Data for the monoclinic crystals were refined to 1.90 A resolution for the complex with (1) (R = 0.178) and to 2.1 A resolution for the complex with (2) (R = 0.193). The effect of the N9-C10 reversed-bridge geometry is to distort the bridge from coplanarity with the pyrido[2,3-d]pyrimidine or quinazoline ring system and to twist the C10 methylene conformation toward a gauche conformation. This change also influences the conformation of the methoxybenzyl ring, moving it away from a trans position. This change places the 5'-methoxy group deeper within the hydrophobic pocket made by Ile65, Pro66 and Phe69 of the pcDHFR active site. These results also revealed the first observation of an unusual conformation for the reversed-bridge geometry (C5-C6-N9-C10 torsion angle) in antifolate (2). The electron density is consistent with the presence of two models (conformers 2-1 and 2-2) that result from inversion of the geometry at N9. The four examples of N9-C10 reversed-bridge antifolates cluster in two conformations, with the structure of quinazoline (1) similar to that previously reported for its 2',5'-dimethoxypyrido[2,3-d]pyrimidine analog (3). The two conformers of (2) differ from these and each other by a twisted-bridge geometry that results in the dimethoxybenzyl ring occupying the same conformational space. Conformer 2-2 also has the N9-C10 reversed bridge perpendicular to the pyrido[2,3-d]pyrimidine plane, in contrast to the gauche-trans conformation normally observed. As a result of these changes, the N9 methyl probes conformational space in the active site not normally occupied by antifolate structures. The N9 methyl of conformer 2-2 makes close contacts to the conserved Leu25 as well as the hydroxyl O atoms of the nicotinamide ribose and Ser64, whereas the other three reversed-bridge conformers make weak hydrophobic contacts with Ile123, Thr61 and Ile65. These antifolates are ten times more selective for pcDHFR than the C9-N10 bridge parent trimetrexate. However, pyrido[2,3-d]pyrimidines (2) and (3) are three times more selective for pcDHFR than quinazoline (1) is for rat liver DHFR. These data suggest that the loss of hydrogen-bonding interactions with N8 is more important to potency than the interactions of the methoxybenzyl substituents.

-	~~{{STRUCTURE_1ly3\| PDB=1ly3 \| SCENE= }}~~	+	Analysis of quinazoline and pyrido[2,3-d]pyrimidine N9-C10 reversed-bridge antifolates in complex with NADP+ and Pneumocystis carinii dihydrofolate reductase.,Cody V, Galitsky N, Luft JR, Pangborn W, Queener SF, Gangjee A Acta Crystallogr D Biol Crystallogr. 2002 Sep;58(Pt 9):1393-9. Epub 2002, Aug 23. PMID:12198294<ref>PMID:12198294</ref>

-	~~===ANALYSIS OF QUINAZOLINE AND PYRIDOPYRIMIDINE N9-C10 REVERSED BRIDGE ANTIFOLATES IN COMPLEX WITH NADP+ AND PNEUMOCYSTIS CARINII DIHYDROFOLATE REDUCTASE===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~{{ABSTRACT_PUBMED_12198294}}~~	+
-		+
-	~~==About this Structure==~~	+
-	~~[[1ly3]] is~~ a ~~1 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Pneumocystis_carinii Pneumocystis carinii]~~. ~~Full crystallographic information is available from [http:~~/~~/oca.weizmann.ac.il/oca-bin/ocashort?id=1LY3 OCA].~~	+

	==See Also==		==See Also==
	*[[Dihydrofolate reductase\|Dihydrofolate reductase]]		*[[Dihydrofolate reductase\|Dihydrofolate reductase]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	<~~ref group="xtra">PMID:012198294<~~/~~ref~~><~~references group="xtra"~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Dihydrofolate reductase]]		[[Category: Dihydrofolate reductase]]
	[[Category: Pneumocystis carinii]]		[[Category: Pneumocystis carinii]]

OCA at 14:51, 20 October 2012

OCA — Sat, 20 Oct 2012 14:51:59 GMT

←Older revision		Revision as of 14:51, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
-	[[1ly3]] is a 1 chain structure ~~of [[Dihydrofolate reductase]]~~ with sequence from [http://en.wikipedia.org/wiki/Pneumocystis_carinii Pneumocystis carinii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LY3 OCA].	+	[[1ly3]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Pneumocystis_carinii Pneumocystis carinii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LY3 OCA].

	==See Also==		==See Also==

OCA at 16:32, 26 July 2012

OCA — Thu, 26 Jul 2012 16:32:32 GMT

←Older revision		Revision as of 16:32, 26 July 2012
Line 1:		Line 1:
	[[Image:1ly3.png\|left\|200px]]		[[Image:1ly3.png\|left\|200px]]

-	<!--
-	The line below this paragraph, containing "STRUCTURE_1ly3", 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.
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	{{STRUCTURE_1ly3\| PDB=1ly3 \| SCENE= }}		{{STRUCTURE_1ly3\| PDB=1ly3 \| SCENE= }}

	===ANALYSIS OF QUINAZOLINE AND PYRIDOPYRIMIDINE N9-C10 REVERSED BRIDGE ANTIFOLATES IN COMPLEX WITH NADP+ AND PNEUMOCYSTIS CARINII DIHYDROFOLATE REDUCTASE===		===ANALYSIS OF QUINAZOLINE AND PYRIDOPYRIMIDINE N9-C10 REVERSED BRIDGE ANTIFOLATES IN COMPLEX WITH NADP+ AND PNEUMOCYSTIS CARINII DIHYDROFOLATE REDUCTASE===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_12198294}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 12198294 is the PubMed ID number.
-	-->
	{{ABSTRACT_PUBMED_12198294}}		{{ABSTRACT_PUBMED_12198294}}

Line 22:		Line 11:

	==See Also==		==See Also==
-	*[[Dihydrofolate reductase]]	+	*[[Dihydrofolate reductase\|Dihydrofolate reductase]]

	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~12198294~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:012198294</ref><references group="xtra"/>
	[[Category: Dihydrofolate reductase]]		[[Category: Dihydrofolate reductase]]
	[[Category: Pneumocystis carinii]]		[[Category: Pneumocystis carinii]]