3fqo - Revision history

OCA at 09:50, 21 February 2024

2024-02-21T09:50:24Z

←Older revision		Revision as of 09:50, 21 February 2024
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	<StructureSection load='3fqo' size='340' side='right'caption='[[3fqo]], [[Resolution\|resolution]] 2.09Å' scene=''>		<StructureSection load='3fqo' size='340' side='right'caption='[[3fqo]], [[Resolution\|resolution]] 2.09Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3fqo]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Staab Staab~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FQO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3FQO FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3fqo]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus_RF122 Staphylococcus aureus RF122]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FQO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3FQO FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=N22:5-[3-(2,5-DIMETHOXYPHENYL)PROP-1-YN-1-YL]-6-ETHYLPYRIMIDINE-2,4-DIAMINE'>N22</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]] 2.09Å</td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3f0b\|3f0b]], [[3f0u\|3f0u]], [[3f0q\|3f0q]], [[3f0v\|3f0v]], [[3f0s\|3f0s]], [[3f0x\|3f0x]], [[3fq0\|3fq0]], [[3fqc\|3fqc]], [[3fqf\|3fqf]], [[3fqv\|3fqv]], [[3fqz\|3fqz]]</div></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=N22:5-[3-(2,5-DIMETHOXYPHENYL)PROP-1-YN-1-YL]-6-ETHYLPYRIMIDINE-2,4-DIAMINE'>N22</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">dfrB, SAB1281c ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=273036 STAAB])</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=3fqo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fqo OCA], [https://pdbe.org/3fqo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3fqo RCSB], [https://www.ebi.ac.uk/pdbsum/3fqo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3fqo 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=3fqo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fqo OCA], [https://pdbe.org/3fqo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3fqo RCSB], [https://www.ebi.ac.uk/pdbsum/3fqo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3fqo ProSAT]</span></td></tr>
	</table>		</table>
-	== Function ==
-	[[https://www.uniprot.org/uniprot/Q2YY41_STAAB Q2YY41_STAAB]] Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis (By similarity).[PIRNR:PIRNR000194]
	== 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=3fqo 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=3fqo ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	Both hospital- and community-acquired Staphylococcus aureus infections have become major health concerns in terms of morbidity, suffering and cost. Trimethoprim-sulfamethoxazole (TMP-SMZ) is an alternative treatment for methicillin-resistant S. aureus (MRSA) infections. However, TMP-resistant strains have arisen with point mutations in dihydrofolate reductase (DHFR), the target for TMP. A single point mutation, F98Y, has been shown biochemically to confer the majority of this resistance to TMP. Using a structure-based approach, we have designed a series of novel propargyl-linked DHFR inhibitors that are active against several trimethoprim-resistant enzymes. We screened this series against wild-type and mutant (F98Y) S. aureus DHFR and found that several are active against both enzymes and specifically that the meta-biphenyl class of these inhibitors is the most potent. In order to understand the structural basis of this potency, we determined eight high-resolution crystal structures: four each of the wild-type and mutant DHFR enzymes bound to various propargyl-linked DHFR inhibitors. In addition to explaining the structure-activity relationships, several of the structures reveal a novel conformation for the cofactor, NADPH. In this new conformation that is predominantly associated with the mutant enzyme, the nicotinamide ring is displaced from its conserved location and three water molecules complete a network of hydrogen bonds between the nicotinamide ring and the protein. In this new position, NADPH has reduced interactions with the inhibitor. An equilibrium between the two conformations of NADPH, implied by their occupancies in the eight crystal structures, is influenced both by the ligand and the F98Y mutation. The mutation induced equilibrium between two NADPH-binding conformations may contribute to decrease TMP binding and thus may be responsible for TMP resistance.
-
-	Crystal structures of wild-type and mutant methicillin-resistant Staphylococcus aureus dihydrofolate reductase reveal an alternate conformation of NADPH that may be linked to trimethoprim resistance.,Frey KM, Liu J, Lombardo MN, Bolstad DB, Wright DL, Anderson AC J Mol Biol. 2009 Apr 17;387(5):1298-308. Epub 2009 Feb 26. PMID:19249312<ref>PMID:19249312</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 3fqo" 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: ~~Staab~~]]	+	[[Category: Staphylococcus aureus RF122]]
-	[[Category: Anderson~~, A C~~]]	+	[[Category: Anderson AC]]
-	[[Category: Frey~~, K M~~]]	+	[[Category: Frey KM]]
-	[[Category: Liu, J]]	+	[[Category: Liu J]]
-	[[Category: Lombardo~~, M N]]~~	+	[[Category: Lombardo MN]]
-	~~[[Category: Oxidoreductase~~]]	+

OCA at 19:57, 20 October 2021

2021-10-20T19:57:44Z

←Older revision		Revision as of 19:57, 20 October 2021
Line 1:		Line 1:

	==Staphylococcus aureus F98Y mutant dihydrofolate reductase complexed with NADPH and 2,4-diamino-5-[3-(2,5-dimethoxyphenyl)prop-1-ynyl]-6-ethylpyrimidine (UCP120B)==		==Staphylococcus aureus F98Y mutant dihydrofolate reductase complexed with NADPH and 2,4-diamino-5-[3-(2,5-dimethoxyphenyl)prop-1-ynyl]-6-ethylpyrimidine (UCP120B)==
-	<StructureSection load='3fqo' size='340' side='right' caption='[[3fqo]], [[Resolution\|resolution]] 2.09Å' scene=''>	+	<StructureSection load='3fqo' size='340' side='right'caption='[[3fqo]], [[Resolution\|resolution]] 2.09Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3fqo]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Staab Staab]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FQO OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3FQO FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3fqo]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Staab Staab]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FQO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3FQO FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=N22:5-[3-(2,5-DIMETHOXYPHENYL)PROP-1-YN-1-YL]-6-ETHYLPYRIMIDINE-2,4-DIAMINE'>N22</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=N22:5-[3-(2,5-DIMETHOXYPHENYL)PROP-1-YN-1-YL]-6-ETHYLPYRIMIDINE-2,4-DIAMINE'>N22</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">[[3f0b\|3f0b]], [[3f0u\|3f0u]], [[3f0q\|3f0q]], [[3f0v\|3f0v]], [[3f0s\|3f0s]], [[3f0x\|3f0x]], [[3fq0\|3fq0]], [[3fqc\|3fqc]], [[3fqf\|3fqf]], [[3fqv\|3fqv]], [[3fqz\|3fqz]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3f0b\|3f0b]], [[3f0u\|3f0u]], [[3f0q\|3f0q]], [[3f0v\|3f0v]], [[3f0s\|3f0s]], [[3f0x\|3f0x]], [[3fq0\|3fq0]], [[3fqc\|3fqc]], [[3fqf\|3fqf]], [[3fqv\|3fqv]], [[3fqz\|3fqz]]</div></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">dfrB, SAB1281c ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=273036 STAAB])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">dfrB, SAB1281c ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=273036 STAAB])</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=3fqo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fqo OCA], [~~http~~://pdbe.org/3fqo PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3fqo RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3fqo PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3fqo 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=3fqo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fqo OCA], [https://pdbe.org/3fqo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3fqo RCSB], [https://www.ebi.ac.uk/pdbsum/3fqo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3fqo ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/Q2YY41_STAAB Q2YY41_STAAB]] Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis (By similarity).[PIRNR:PIRNR000194]	+	[[https://www.uniprot.org/uniprot/Q2YY41_STAAB Q2YY41_STAAB]] Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis (By similarity).[PIRNR:PIRNR000194]
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fq/3fqo_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fq/3fqo_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 31:		Line 31:
	</div>		</div>
	<div class="pdbe-citations 3fqo" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 3fqo" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Dihydrofolate reductase 3D structures\|Dihydrofolate reductase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
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	</StructureSection>		</StructureSection>
	[[Category: Dihydrofolate reductase]]		[[Category: Dihydrofolate reductase]]
		+	[[Category: Large Structures]]
	[[Category: Staab]]		[[Category: Staab]]
	[[Category: Anderson, A C]]		[[Category: Anderson, A C]]

OCA at 06:47, 1 November 2017

2017-11-01T06:47:50Z

←Older revision		Revision as of 06:47, 1 November 2017
Line 1:		Line 1:
		+
	==Staphylococcus aureus F98Y mutant dihydrofolate reductase complexed with NADPH and 2,4-diamino-5-[3-(2,5-dimethoxyphenyl)prop-1-ynyl]-6-ethylpyrimidine (UCP120B)==		==Staphylococcus aureus F98Y mutant dihydrofolate reductase complexed with NADPH and 2,4-diamino-5-[3-(2,5-dimethoxyphenyl)prop-1-ynyl]-6-ethylpyrimidine (UCP120B)==
	<StructureSection load='3fqo' size='340' side='right' caption='[[3fqo]], [[Resolution\|resolution]] 2.09Å' scene=''>		<StructureSection load='3fqo' size='340' side='right' caption='[[3fqo]], [[Resolution\|resolution]] 2.09Å' scene=''>
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	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">dfrB, SAB1281c ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=273036 STAAB])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">dfrB, SAB1281c ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=273036 STAAB])</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=3fqo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fqo OCA], [http://pdbe.org/3fqo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3fqo RCSB], [http://www.ebi.ac.uk/pdbsum/3fqo 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=3fqo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fqo OCA], [http://pdbe.org/3fqo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3fqo RCSB], [http://www.ebi.ac.uk/pdbsum/3fqo PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3fqo ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 30:		Line 31:
	</div>		</div>
	<div class="pdbe-citations 3fqo" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 3fqo" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[Dihydrofolate reductase\|Dihydrofolate reductase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 10:54, 7 February 2016

2016-02-07T10:54:58Z

←Older revision		Revision as of 10:54, 7 February 2016
Line 7:		Line 7:
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">dfrB, SAB1281c ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=273036 STAAB])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">dfrB, SAB1281c ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=273036 STAAB])</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=3fqo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fqo OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3fqo RCSB], [http://www.ebi.ac.uk/pdbsum/3fqo 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=3fqo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fqo OCA], [http://pdbe.org/3fqo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3fqo RCSB], [http://www.ebi.ac.uk/pdbsum/3fqo PDBsum]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
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=3fqo ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
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	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 3fqo" style="background-color:#fffaf0;"></div>

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

OCA at 14:33, 24 December 2014

2014-12-24T14:33:56Z

←Older revision		Revision as of 14:33, 24 December 2014
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-	~~{{STRUCTURE_3fqo\| PDB=3fqo \| SCENE= }}~~	+	==Staphylococcus aureus F98Y mutant dihydrofolate reductase complexed with NADPH and 2,4-diamino-5-[3-(2,5-dimethoxyphenyl)prop-1-ynyl]-6-ethylpyrimidine (UCP120B)==
-	===Staphylococcus aureus F98Y mutant dihydrofolate reductase complexed with NADPH and 2,4-diamino-5-[3-(2,5-dimethoxyphenyl)prop-1-ynyl]-6-ethylpyrimidine (UCP120B)===	+	<StructureSection load='3fqo' size='340' side='right' caption='[[3fqo]], [[Resolution\|resolution]] 2.09Å' scene=''>
-	~~{{ABSTRACT_PUBMED_19249312}}~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[3fqo]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Staab Staab]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FQO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3FQO FirstGlance]. <br>
-	==Function==	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=N22:5-[3-(2,5-DIMETHOXYPHENYL)PROP-1-YN-1-YL]-6-ETHYLPYRIMIDINE-2,4-DIAMINE'>N22</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">[[3f0b\|3f0b]], [[3f0u\|3f0u]], [[3f0q\|3f0q]], [[3f0v\|3f0v]], [[3f0s\|3f0s]], [[3f0x\|3f0x]], [[3fq0\|3fq0]], [[3fqc\|3fqc]], [[3fqf\|3fqf]], [[3fqv\|3fqv]], [[3fqz\|3fqz]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">dfrB, SAB1281c ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=273036 STAAB])</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=3fqo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fqo OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3fqo RCSB], [http://www.ebi.ac.uk/pdbsum/3fqo PDBsum]</span></td></tr>
		+	</table>
		+	== Function ==
	[[http://www.uniprot.org/uniprot/Q2YY41_STAAB Q2YY41_STAAB]] Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis (By similarity).[PIRNR:PIRNR000194]		[[http://www.uniprot.org/uniprot/Q2YY41_STAAB Q2YY41_STAAB]] Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis (By similarity).[PIRNR:PIRNR000194]
		+	== 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/fq/3fqo_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 ==
		+	Both hospital- and community-acquired Staphylococcus aureus infections have become major health concerns in terms of morbidity, suffering and cost. Trimethoprim-sulfamethoxazole (TMP-SMZ) is an alternative treatment for methicillin-resistant S. aureus (MRSA) infections. However, TMP-resistant strains have arisen with point mutations in dihydrofolate reductase (DHFR), the target for TMP. A single point mutation, F98Y, has been shown biochemically to confer the majority of this resistance to TMP. Using a structure-based approach, we have designed a series of novel propargyl-linked DHFR inhibitors that are active against several trimethoprim-resistant enzymes. We screened this series against wild-type and mutant (F98Y) S. aureus DHFR and found that several are active against both enzymes and specifically that the meta-biphenyl class of these inhibitors is the most potent. In order to understand the structural basis of this potency, we determined eight high-resolution crystal structures: four each of the wild-type and mutant DHFR enzymes bound to various propargyl-linked DHFR inhibitors. In addition to explaining the structure-activity relationships, several of the structures reveal a novel conformation for the cofactor, NADPH. In this new conformation that is predominantly associated with the mutant enzyme, the nicotinamide ring is displaced from its conserved location and three water molecules complete a network of hydrogen bonds between the nicotinamide ring and the protein. In this new position, NADPH has reduced interactions with the inhibitor. An equilibrium between the two conformations of NADPH, implied by their occupancies in the eight crystal structures, is influenced both by the ligand and the F98Y mutation. The mutation induced equilibrium between two NADPH-binding conformations may contribute to decrease TMP binding and thus may be responsible for TMP resistance.

-	~~==About this Structure==~~	+	Crystal structures of wild-type and mutant methicillin-resistant Staphylococcus aureus dihydrofolate reductase reveal an alternate conformation of NADPH that may be linked to trimethoprim resistance.,Frey KM, Liu J, Lombardo MN, Bolstad DB, Wright DL, Anderson AC J Mol Biol. 2009 Apr 17;387(5):1298-308. Epub 2009 Feb 26. PMID:19249312<ref>PMID:19249312</ref>
-	~~[[3fqo]] is a 1 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Staab Staab]~~. ~~Full crystallographic information is available from [http~~://~~oca~~.~~weizmann~~.ac.il/~~oca-bin/ocashort?id=3FQO OCA].~~	+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>

	==See Also==		==See Also==
	*[[Dihydrofolate reductase\|Dihydrofolate reductase]]		*[[Dihydrofolate reductase\|Dihydrofolate reductase]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	~~<ref group="xtra">PMID:019249312</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Dihydrofolate reductase]]		[[Category: Dihydrofolate reductase]]
	[[Category: Staab]]		[[Category: Staab]]
-	[[Category: Anderson, A C.]]	+	[[Category: Anderson, A C]]
-	[[Category: Frey, K M.]]	+	[[Category: Frey, K M]]
-	[[Category: Liu, J.]]	+	[[Category: Liu, J]]
-	[[Category: Lombardo, M N.]]	+	[[Category: Lombardo, M N]]
	[[Category: Oxidoreductase]]		[[Category: Oxidoreductase]]

OCA at 08:54, 27 November 2013

2013-11-27T08:54:43Z

←Older revision		Revision as of 08:54, 27 November 2013
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-	[[Image:3fqo.png\|left\|200px]]
-
	{{STRUCTURE_3fqo\| PDB=3fqo \| SCENE= }}		{{STRUCTURE_3fqo\| PDB=3fqo \| SCENE= }}
-
	===Staphylococcus aureus F98Y mutant dihydrofolate reductase complexed with NADPH and 2,4-diamino-5-[3-(2,5-dimethoxyphenyl)prop-1-ynyl]-6-ethylpyrimidine (UCP120B)===		===Staphylococcus aureus F98Y mutant dihydrofolate reductase complexed with NADPH and 2,4-diamino-5-[3-(2,5-dimethoxyphenyl)prop-1-ynyl]-6-ethylpyrimidine (UCP120B)===
		+	{{ABSTRACT_PUBMED_19249312}}

-	~~{{ABSTRACT_PUBMED_19249312}}~~	+	==Function==
		+	[[http://www.uniprot.org/uniprot/Q2YY41_STAAB Q2YY41_STAAB]] Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis (By similarity).[PIRNR:PIRNR000194]

	==About this Structure==		==About this Structure==
-	[[3fqo]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Staphylococcus_aureus_rf122 Staphylococcus aureus rf122~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FQO OCA].	+	[[3fqo]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Staab Staab]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FQO OCA].

	==See Also==		==See Also==
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	==Reference==		==Reference==
-	<ref group="xtra">PMID:019249312</ref><references group="xtra"/>	+	<ref group="xtra">PMID:019249312</ref><references group="xtra"/><references/>
	[[Category: Dihydrofolate reductase]]		[[Category: Dihydrofolate reductase]]
-	[[Category: ~~Staphylococcus aureus rf122~~]]	+	[[Category: Staab]]
	[[Category: Anderson, A C.]]		[[Category: Anderson, A C.]]
	[[Category: Frey, K M.]]		[[Category: Frey, K M.]]

OCA at 06:25, 20 October 2012

2012-10-20T06:25:19Z

←Older revision		Revision as of 06:25, 20 October 2012
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	==About this Structure==		==About this Structure==
-	[[3fqo]] is a 1 chain structure ~~of [[Dihydrofolate reductase]]~~ with sequence from [http://en.wikipedia.org/wiki/Staphylococcus_aureus_rf122 Staphylococcus aureus rf122]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FQO OCA].	+	[[3fqo]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Staphylococcus_aureus_rf122 Staphylococcus aureus rf122]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FQO OCA].

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

OCA at 13:08, 25 July 2012

2012-07-25T13:08:40Z

←Older revision		Revision as of 13:08, 25 July 2012
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	[[Image:3fqo.png\|left\|200px]]		[[Image:3fqo.png\|left\|200px]]

-	<!--
-	The line below this paragraph, containing "STRUCTURE_3fqo", 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),
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	{{STRUCTURE_3fqo\| PDB=3fqo \| SCENE= }}		{{STRUCTURE_3fqo\| PDB=3fqo \| SCENE= }}

	===Staphylococcus aureus F98Y mutant dihydrofolate reductase complexed with NADPH and 2,4-diamino-5-[3-(2,5-dimethoxyphenyl)prop-1-ynyl]-6-ethylpyrimidine (UCP120B)===		===Staphylococcus aureus F98Y mutant dihydrofolate reductase complexed with NADPH and 2,4-diamino-5-[3-(2,5-dimethoxyphenyl)prop-1-ynyl]-6-ethylpyrimidine (UCP120B)===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_19249312}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 19249312 is the PubMed ID number.
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	{{ABSTRACT_PUBMED_19249312}}		{{ABSTRACT_PUBMED_19249312}}

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

	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~19249312~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:019249312</ref><references group="xtra"/>
	[[Category: Dihydrofolate reductase]]		[[Category: Dihydrofolate reductase]]
	[[Category: Staphylococcus aureus rf122]]		[[Category: Staphylococcus aureus rf122]]

OCA: Protected "3fqo" [edit=sysop:move=sysop]

2010-12-27T00:05:00Z

Protected "3fqo" [edit=sysop:move=sysop]

←Older revision

Revision as of 00:05, 27 December 2010

OCA at 00:04, 27 December 2010

2010-12-27T00:04:59Z

←Older revision		Revision as of 00:04, 27 December 2010
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-	{{Seed}}
	[[Image:3fqo.png\|left\|200px]]		[[Image:3fqo.png\|left\|200px]]

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	==About this Structure==		==About this Structure==
-	~~3FQO~~ is a 1 chain structure of sequence from [http://en.wikipedia.org/wiki/Staphylococcus_aureus_rf122 Staphylococcus aureus rf122]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FQO OCA].	+	[[3fqo]] is a 1 chain structure of [[Dihydrofolate reductase]] with sequence from [http://en.wikipedia.org/wiki/Staphylococcus_aureus_rf122 Staphylococcus aureus rf122]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FQO OCA].
		+
		+	==See Also==
		+	*[[Dihydrofolate reductase]]

	==Reference==		==Reference==
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	[[Category: Lombardo, M N.]]		[[Category: Lombardo, M N.]]
	[[Category: Oxidoreductase]]		[[Category: Oxidoreductase]]
-
-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Apr 22 10:48:46 2009''