2anq - Revision history

OCA at 09:13, 14 February 2024

OCA — Wed, 14 Feb 2024 09:13:38 GMT

←Older revision		Revision as of 09:13, 14 February 2024
Line 3:		Line 3:
	<StructureSection load='2anq' size='340' side='right'caption='[[2anq]], [[Resolution\|resolution]] 2.13Å' scene=''>		<StructureSection load='2anq' size='340' side='right'caption='[[2anq]], [[Resolution\|resolution]] 2.13Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2anq]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/~~"bacillus_coli"_migula_1895 "bacillus~~ coli~~" migula 1895~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ANQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ANQ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2anq]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ANQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ANQ FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=C1A:(2,5-DIMETHYLBENZENE-1,4-DIYL)DIMETHANEDIYL+BIS(N-CARBAMIMIDOYLCARBAMIMIDOTHIOATE)'>C1A</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</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]] 2.13Å</td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2ano\|2ano]]</div></td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=C1A:(2,5-DIMETHYLBENZENE-1,4-DIYL)DIMETHANEDIYL+BIS(N-CARBAMIMIDOYLCARBAMIMIDOTHIOATE)'>C1A</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">folA, tmrA ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</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=2anq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2anq OCA], [https://pdbe.org/2anq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2anq RCSB], [https://www.ebi.ac.uk/pdbsum/2anq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2anq 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=2anq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2anq OCA], [https://pdbe.org/2anq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2anq RCSB], [https://www.ebi.ac.uk/pdbsum/2anq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2anq ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/DYR_ECOLI DYR_ECOLI]] 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_ECOLI DYR_ECOLI] 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 22:		Line 20:
	</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=2anq 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=2anq ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	Dihydrofolate reductase (DHFR) is a vital metabolic enzyme and thus a clinically prominent target in the design of antimetabolites. In this work, we identify 1,4-bis-{[N-(1-imino-1-guanidino-methyl)]sulfanylmethyl}-3,6-dimethyl-benz ene (compound 1) as the correct structure of the previously reported DHFR inhibitor 1,4-bis-{(iminothioureidomethyl)aminomethyl}-3,6-dimethyl-benzene (compound 2). The fact that compound 1 has an uncharacteristic structure for DHFR inhibitors, and an affinity (KI of 11.5 nM) comparable to potent inhibitors such as methotrexate and trimethoprim, made this inhibitor of interest for further analysis. We have conducted a characterization of the primary interactions of compound 1 and DHFR using a combination of X-ray structure and SAR analysis. The crystal structure of E. coli DHFR in complex with compound 1 and NADPH reveals that one portion of this inhibitor exploits a unique binding surface, the M20 loop. The importance of this interface was further confirmed by SAR analysis and additional structural characterization.
-
-	A 2.13 A structure of E. coli dihydrofolate reductase bound to a novel competitive inhibitor reveals a new binding surface involving the M20 loop region.,Summerfield RL, Daigle DM, Mayer S, Mallik D, Hughes DW, Jackson SG, Sulek M, Organ MG, Brown ED, Junop MS J Med Chem. 2006 Nov 30;49(24):6977-86. PMID:17125251<ref>PMID:17125251</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 2anq" 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: ~~Bacillus~~ coli ~~migula 1895]]~~	+	[[Category: Escherichia coli]]
-	~~[[Category: Dihydrofolate reductase~~]]	+
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Brown~~, E D~~]]	+	[[Category: Brown ED]]
-	[[Category: Daigle~~, D M~~]]	+	[[Category: Daigle DM]]
-	[[Category: Hughes~~, D W~~]]	+	[[Category: Hughes DW]]
-	[[Category: Jackson~~, S G~~]]	+	[[Category: Jackson SG]]
-	[[Category: Junop~~, M S~~]]	+	[[Category: Junop MS]]
-	[[Category: Mayer, S]]	+	[[Category: Mayer S]]
-	[[Category: Organ, M]]	+	[[Category: Organ M]]
-	[[Category: Summerfield~~, R L]]~~	+	[[Category: Summerfield RL]]
-	~~[[Category: Dhfr]]~~	+
-	~~[[Category: Oxidoreductase]]~~	+
-	~~[[Category: Protein inhibitor complex~~]]	+

OCA at 08:34, 27 January 2021

OCA — Wed, 27 Jan 2021 08:34:25 GMT

←Older revision		Revision as of 08:34, 27 January 2021
Line 1:		Line 1:

	==Crystal Structure of E.coli DHFR in complex with NADPH and the inhibitor compound 10a.==		==Crystal Structure of E.coli DHFR in complex with NADPH and the inhibitor compound 10a.==
-	<StructureSection load='2anq' size='340' side='right' caption='[[2anq]], [[Resolution\|resolution]] 2.13Å' scene=''>	+	<StructureSection load='2anq' size='340' side='right'caption='[[2anq]], [[Resolution\|resolution]] 2.13Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2anq]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ANQ OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=2ANQ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2anq]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ANQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ANQ FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=C1A:(2,5-DIMETHYLBENZENE-1,4-DIYL)DIMETHANEDIYL+BIS(N-CARBAMIMIDOYLCARBAMIMIDOTHIOATE)'>C1A</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=C1A:(2,5-DIMETHYLBENZENE-1,4-DIYL)DIMETHANEDIYL+BIS(N-CARBAMIMIDOYLCARBAMIMIDOTHIOATE)'>C1A</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2ano\|2ano]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2ano\|2ano]]</div></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">folA, tmrA ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">folA, tmrA ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</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=2anq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2anq OCA], [~~http~~://pdbe.org/2anq PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=2anq RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/2anq PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=2anq 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=2anq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2anq OCA], [https://pdbe.org/2anq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2anq RCSB], [https://www.ebi.ac.uk/pdbsum/2anq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2anq ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/DYR_ECOLI DYR_ECOLI]] 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_ECOLI DYR_ECOLI]] 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 33:		Line 33:

	==See Also==		==See Also==
-	*[[Dihydrofolate reductase\|Dihydrofolate reductase]]	+	*[[Dihydrofolate reductase 3D structures\|Dihydrofolate reductase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 40:		Line 40:
	[[Category: Bacillus coli migula 1895]]		[[Category: Bacillus coli migula 1895]]
	[[Category: Dihydrofolate reductase]]		[[Category: Dihydrofolate reductase]]
		+	[[Category: Large Structures]]
	[[Category: Brown, E D]]		[[Category: Brown, E D]]
	[[Category: Daigle, D M]]		[[Category: Daigle, D M]]

OCA at 07:23, 9 May 2018

OCA — Wed, 09 May 2018 07:23:15 GMT

←Older revision		Revision as of 07:23, 9 May 2018
Line 1:		Line 1:
		+
	==Crystal Structure of E.coli DHFR in complex with NADPH and the inhibitor compound 10a.==		==Crystal Structure of E.coli DHFR in complex with NADPH and the inhibitor compound 10a.==
	<StructureSection load='2anq' size='340' side='right' caption='[[2anq]], [[Resolution\|resolution]] 2.13Å' scene=''>		<StructureSection load='2anq' size='340' side='right' caption='[[2anq]], [[Resolution\|resolution]] 2.13Å' scene=''>
Line 7:		Line 8:
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">folA, tmrA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">folA, tmrA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</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=2anq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2anq OCA], [http://pdbe.org/2anq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2anq RCSB], [http://www.ebi.ac.uk/pdbsum/2anq 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=2anq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2anq OCA], [http://pdbe.org/2anq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2anq RCSB], [http://www.ebi.ac.uk/pdbsum/2anq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2anq ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 15:		Line 16:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/an/2anq_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/an/2anq_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>

OCA at 03:18, 8 February 2016

OCA — Mon, 08 Feb 2016 03:18:05 GMT

←Older revision		Revision as of 03:18, 8 February 2016
Line 19:		Line 19:
	<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=2anq ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">

OCA at 07:21, 10 September 2015

OCA — Thu, 10 Sep 2015 07:21:47 GMT

←Older revision		Revision as of 07:21, 10 September 2015
Line 7:		Line 7:
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">folA, tmrA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">folA, tmrA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</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=2anq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2anq OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2anq RCSB], [http://www.ebi.ac.uk/pdbsum/2anq 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=2anq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2anq OCA], [http://pdbe.org/2anq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2anq RCSB], [http://www.ebi.ac.uk/pdbsum/2anq PDBsum]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 29:		Line 29:
	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 2anq" style="background-color:#fffaf0;"></div>

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

OCA at 20:11, 24 December 2014

OCA — Wed, 24 Dec 2014 20:11:52 GMT

←Older revision		Revision as of 20:11, 24 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2anq]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ANQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ANQ FirstGlance]. <br>		<table><tr><td colspan='2'>[[2anq]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ANQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ANQ FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=C1A:(2,5-DIMETHYLBENZENE-1,4-DIYL)DIMETHANEDIYL+BIS(N-CARBAMIMIDOYLCARBAMIMIDOTHIOATE)'>C1A</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=C1A:(2,5-DIMETHYLBENZENE-1,4-DIYL)DIMETHANEDIYL+BIS(N-CARBAMIMIDOYLCARBAMIMIDOTHIOATE)'>C1A</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2ano\|2ano]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2ano\|2ano]]</td></tr>
-	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">folA, tmrA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">folA, tmrA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</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=2anq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2anq OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2anq RCSB], [http://www.ebi.ac.uk/pdbsum/2anq 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=2anq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2anq OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2anq RCSB], [http://www.ebi.ac.uk/pdbsum/2anq PDBsum]</span></td></tr>
-	<table>	+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/DYR_ECOLI DYR_ECOLI]] 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 36:		Line 38:
	[[Category: Bacillus coli migula 1895]]		[[Category: Bacillus coli migula 1895]]
	[[Category: Dihydrofolate reductase]]		[[Category: Dihydrofolate reductase]]
-	[[Category: Brown, E D.]]	+	[[Category: Brown, E D]]
-	[[Category: Daigle, D M.]]	+	[[Category: Daigle, D M]]
-	[[Category: Hughes, D W.]]	+	[[Category: Hughes, D W]]
-	[[Category: Jackson, S G.]]	+	[[Category: Jackson, S G]]
-	[[Category: Junop, M S.]]	+	[[Category: Junop, M S]]
-	[[Category: Mayer, S.]]	+	[[Category: Mayer, S]]
-	[[Category: Organ, M.]]	+	[[Category: Organ, M]]
-	[[Category: Summerfield, R L.]]	+	[[Category: Summerfield, R L]]
	[[Category: Dhfr]]		[[Category: Dhfr]]
	[[Category: Oxidoreductase]]		[[Category: Oxidoreductase]]
	[[Category: Protein inhibitor complex]]		[[Category: Protein inhibitor complex]]

OCA at 10:31, 3 October 2014

OCA — Fri, 03 Oct 2014 10:31:38 GMT

←Older revision		Revision as of 10:31, 3 October 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_2anq\| PDB=2anq \| SCENE= }}~~	+	==Crystal Structure of E.coli DHFR in complex with NADPH and the inhibitor compound 10a.==
-	===Crystal Structure of E.coli DHFR in complex with NADPH and the inhibitor compound 10a.===	+	<StructureSection load='2anq' size='340' side='right' caption='[[2anq]], [[Resolution\|resolution]] 2.13Å' scene=''>
-	{{~~ABSTRACT_PUBMED_17125251}~~}	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[2anq]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ANQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ANQ FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=C1A:(2,5-DIMETHYLBENZENE-1,4-DIYL)DIMETHANEDIYL+BIS(N-CARBAMIMIDOYLCARBAMIMIDOTHIOATE)'>C1A</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2ano\|2ano]]</td></tr>
		+	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">folA, tmrA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</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=2anq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2anq OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2anq RCSB], [http://www.ebi.ac.uk/pdbsum/2anq 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/an/2anq_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 ==
		+	Dihydrofolate reductase (DHFR) is a vital metabolic enzyme and thus a clinically prominent target in the design of antimetabolites. In this work, we identify 1,4-bis-{[N-(1-imino-1-guanidino-methyl)]sulfanylmethyl}-3,6-dimethyl-benz ene (compound 1) as the correct structure of the previously reported DHFR inhibitor 1,4-bis-{(iminothioureidomethyl)aminomethyl}-3,6-dimethyl-benzene (compound 2). The fact that compound 1 has an uncharacteristic structure for DHFR inhibitors, and an affinity (KI of 11.5 nM) comparable to potent inhibitors such as methotrexate and trimethoprim, made this inhibitor of interest for further analysis. We have conducted a characterization of the primary interactions of compound 1 and DHFR using a combination of X-ray structure and SAR analysis. The crystal structure of E. coli DHFR in complex with compound 1 and NADPH reveals that one portion of this inhibitor exploits a unique binding surface, the M20 loop. The importance of this interface was further confirmed by SAR analysis and additional structural characterization.

-	~~==Function==~~	+	A 2.13 A structure of E. coli dihydrofolate reductase bound to a novel competitive inhibitor reveals a new binding surface involving the M20 loop region.,Summerfield RL, Daigle DM, Mayer S, Mallik D, Hughes DW, Jackson SG, Sulek M, Organ MG, Brown ED, Junop MS J Med Chem. 2006 Nov 30;49(24):6977-86. PMID:17125251<ref>PMID:17125251</ref>
-	~~[[http://www~~.~~uniprot~~.~~org/uniprot/DYR_ECOLI DYR_ECOLI]] Key enzyme in folate metabolism~~. ~~Catalyzes an essential reaction for de novo glycine and purine synthesis~~, ~~and for DNA precursor synthesis~~.	+

-	~~==About this Structure==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[2anq]] is~~ a ~~1 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895]~~. ~~Full crystallographic information is available from [http:~~/~~/oca.weizmann.ac.il/oca-bin/ocashort?id=2ANQ OCA].~~	+	</div>

	==See Also==		==See Also==
	*[[Dihydrofolate reductase\|Dihydrofolate reductase]]		*[[Dihydrofolate reductase\|Dihydrofolate reductase]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	~~<ref group="xtra">PMID:017125251</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Bacillus coli migula 1895]]		[[Category: Bacillus coli migula 1895]]
	[[Category: Dihydrofolate reductase]]		[[Category: Dihydrofolate reductase]]

OCA at 12:12, 20 November 2013

OCA — Wed, 20 Nov 2013 12:12:30 GMT

←Older revision		Revision as of 12:12, 20 November 2013
Line 1:		Line 1:
-	[[Image:2anq.png\|left\|200px]]
-
	{{STRUCTURE_2anq\| PDB=2anq \| SCENE= }}		{{STRUCTURE_2anq\| PDB=2anq \| SCENE= }}
-
	===Crystal Structure of E.coli DHFR in complex with NADPH and the inhibitor compound 10a.===		===Crystal Structure of E.coli DHFR in complex with NADPH and the inhibitor compound 10a.===
		+	{{ABSTRACT_PUBMED_17125251}}

-	~~{{ABSTRACT_PUBMED_17125251}}~~	+	==Function==
		+	[[http://www.uniprot.org/uniprot/DYR_ECOLI DYR_ECOLI]] Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis.

	==About this Structure==		==About this Structure==
-	[[2anq]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Escherichia_coli Escherichia~~ coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ANQ OCA].	+	[[2anq]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ANQ OCA].

	==See Also==		==See Also==
Line 14:		Line 13:

	==Reference==		==Reference==
-	<ref group="xtra">PMID:017125251</ref><references group="xtra"/>	+	<ref group="xtra">PMID:017125251</ref><references group="xtra"/><references/>
		+	[[Category: Bacillus coli migula 1895]]
	[[Category: Dihydrofolate reductase]]		[[Category: Dihydrofolate reductase]]
-	[[Category: Escherichia coli]]
	[[Category: Brown, E D.]]		[[Category: Brown, E D.]]
	[[Category: Daigle, D M.]]		[[Category: Daigle, D M.]]

OCA at 08:43, 20 October 2012

OCA — Sat, 20 Oct 2012 08:43:58 GMT

←Older revision		Revision as of 08:43, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
-	[[2anq]] is a 1 chain structure ~~of [[Dihydrofolate reductase]]~~ with sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ANQ OCA].	+	[[2anq]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ANQ OCA].

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

OCA at 20:35, 25 July 2012

OCA — Wed, 25 Jul 2012 20:35:26 GMT

←Older revision		Revision as of 20:35, 25 July 2012
Line 1:		Line 1:
	[[Image:2anq.png\|left\|200px]]		[[Image:2anq.png\|left\|200px]]

-	<!--
-	The line below this paragraph, containing "STRUCTURE_2anq", 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_2anq\| PDB=2anq \| SCENE= }}		{{STRUCTURE_2anq\| PDB=2anq \| SCENE= }}

	===Crystal Structure of E.coli DHFR in complex with NADPH and the inhibitor compound 10a.===		===Crystal Structure of E.coli DHFR in complex with NADPH and the inhibitor compound 10a.===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_17125251}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 17125251 is the PubMed ID number.
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	{{ABSTRACT_PUBMED_17125251}}		{{ABSTRACT_PUBMED_17125251}}

Line 22:		Line 11:

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

	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~17125251~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:017125251</ref><references group="xtra"/>
	[[Category: Dihydrofolate reductase]]		[[Category: Dihydrofolate reductase]]
	[[Category: Escherichia coli]]		[[Category: Escherichia coli]]