4tu5 - Revision history

OCA at 07:23, 27 September 2023

OCA — Wed, 27 Sep 2023 07:23:22 GMT

←Older revision		Revision as of 07:23, 27 September 2023
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4tu5]] 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=4TU5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4TU5 FirstGlance]. <br>		<table><tr><td colspan='2'>[[4tu5]] 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=4TU5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4TU5 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=06W:6-ETHYL-5-{(3S)-3-[3-METHOXY-5-(PYRIDIN-4-YL)PHENYL]BUT-1-YN-1-YL}PYRIMIDINE-2,4-DIAMINE'>06W</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]] 2.161Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=06W:6-ETHYL-5-{(3S)-3-[3-METHOXY-5-(PYRIDIN-4-YL)PHENYL]BUT-1-YN-1-YL}PYRIMIDINE-2,4-DIAMINE'>06W</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene></td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4tu5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4tu5 OCA], [https://pdbe.org/4tu5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4tu5 RCSB], [https://www.ebi.ac.uk/pdbsum/4tu5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4tu5 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=4tu5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4tu5 OCA], [https://pdbe.org/4tu5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4tu5 RCSB], [https://www.ebi.ac.uk/pdbsum/4tu5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4tu5 ProSAT]</span></td></tr>
	</table>		</table>

OCA at 10:55, 15 March 2023

OCA — Wed, 15 Mar 2023 10:55:57 GMT

←Older revision		Revision as of 10:55, 15 March 2023
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	<StructureSection load='4tu5' size='340' side='right'caption='[[4tu5]], [[Resolution\|resolution]] 2.16Å' scene=''>		<StructureSection load='4tu5' size='340' side='right'caption='[[4tu5]], [[Resolution\|resolution]] 2.16Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4tu5]] 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=4TU5 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4TU5 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4tu5]] 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=4TU5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4TU5 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=06W:6-ETHYL-5-{(3S)-3-[3-METHOXY-5-(PYRIDIN-4-YL)PHENYL]BUT-1-YN-1-YL}PYRIMIDINE-2,4-DIAMINE'>06W</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=06W:6-ETHYL-5-{(3S)-3-[3-METHOXY-5-(PYRIDIN-4-YL)PHENYL]BUT-1-YN-1-YL}PYRIMIDINE-2,4-DIAMINE'>06W</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">[[4tu2\|4tu2]]</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=4tu5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4tu5 OCA], [https://pdbe.org/4tu5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4tu5 RCSB], [https://www.ebi.ac.uk/pdbsum/4tu5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4tu5 ProSAT]</span></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=4tu5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4tu5 OCA], [~~http~~://pdbe.org/4tu5 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4tu5 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4tu5 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4tu5 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/A0A0M3KKX1_STAAB A0A0M3KKX1_STAAB] Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis.[PIRNR:PIRNR000194]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	__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: Reeve~~, S M]]~~	+	[[Category: Reeve SM]]
-	~~[[Category: Antifolate]]~~	+
-	~~[[Category: Enantiopure inhibitor]]~~	+
-	~~[[Category: Methicillin-resistant staphylococcus aureus]]~~	+
-	~~[[Category: Oxidoreductase]]~~	+
-	~~[[Category: Oxidoreductase-oxidoreductase inhibitor complex~~]]	+

OCA at 15:38, 11 December 2019

OCA — Wed, 11 Dec 2019 15:38:45 GMT

←Older revision		Revision as of 15:38, 11 December 2019
Line 1:		Line 1:

	==Staphylococcus aureus Dihydrofolate Reductase complexed with NADPH and 6-ETHYL-5-[(3S)-3-[3-METHOXY-5-(PYRIDIN-4-YL)PHENYL]BUT-1-YN-1-YL]PYRIMIDINE-2,4-DIAMINE (UCP1062)==		==Staphylococcus aureus Dihydrofolate Reductase complexed with NADPH and 6-ETHYL-5-[(3S)-3-[3-METHOXY-5-(PYRIDIN-4-YL)PHENYL]BUT-1-YN-1-YL]PYRIMIDINE-2,4-DIAMINE (UCP1062)==
-	<StructureSection load='4tu5' size='340' side='right' caption='[[4tu5]], [[Resolution\|resolution]] 2.16Å' scene=''>	+	<StructureSection load='4tu5' size='340' side='right'caption='[[4tu5]], [[Resolution\|resolution]] 2.16Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4tu5]] 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=4TU5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4TU5 FirstGlance]. <br>		<table><tr><td colspan='2'>[[4tu5]] 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=4TU5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4TU5 FirstGlance]. <br>
Line 21:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 4tu5" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4tu5" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Dihydrofolate reductase 3D structures\|Dihydrofolate reductase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 26:		Line 29:
	</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 12:04, 6 November 2017

OCA — Mon, 06 Nov 2017 12:04:33 GMT

←Older revision		Revision as of 12:04, 6 November 2017
Line 3:		Line 3:
	<StructureSection load='4tu5' size='340' side='right' caption='[[4tu5]], [[Resolution\|resolution]] 2.16Å' scene=''>		<StructureSection load='4tu5' size='340' side='right' caption='[[4tu5]], [[Resolution\|resolution]] 2.16Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4tu5]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4TU5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4TU5 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4tu5]] 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=4TU5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4TU5 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=06W:6-ETHYL-5-{(3S)-3-[3-METHOXY-5-(PYRIDIN-4-YL)PHENYL]BUT-1-YN-1-YL}PYRIMIDINE-2,4-DIAMINE'>06W</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"><scene name='pdbligand=06W:6-ETHYL-5-{(3S)-3-[3-METHOXY-5-(PYRIDIN-4-YL)PHENYL]BUT-1-YN-1-YL}PYRIMIDINE-2,4-DIAMINE'>06W</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">[[4tu2\|4tu2]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4tu2\|4tu2]]</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=4tu5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4tu5 OCA], [http://pdbe.org/4tu5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4tu5 RCSB], [http://www.ebi.ac.uk/pdbsum/4tu5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4tu5 ProSAT]</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=4tu5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4tu5 OCA], [http://pdbe.org/4tu5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4tu5 RCSB], [http://www.ebi.ac.uk/pdbsum/4tu5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4tu5 ProSAT]</span></td></tr>
Line 20:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 4tu5" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4tu5" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[Dihydrofolate reductase\|Dihydrofolate reductase]]
	== References ==		== References ==
	<references/>		<references/>
Line 28:		Line 26:
	</StructureSection>		</StructureSection>
	[[Category: Dihydrofolate reductase]]		[[Category: Dihydrofolate reductase]]
		+	[[Category: Staab]]
	[[Category: Anderson, A C]]		[[Category: Anderson, A C]]
	[[Category: Reeve, S M]]		[[Category: Reeve, S M]]

OCA at 13:31, 4 May 2017

OCA — Thu, 04 May 2017 13:31:05 GMT

←Older revision		Revision as of 13:31, 4 May 2017
Line 1:		Line 1:
		+
	==Staphylococcus aureus Dihydrofolate Reductase complexed with NADPH and 6-ETHYL-5-[(3S)-3-[3-METHOXY-5-(PYRIDIN-4-YL)PHENYL]BUT-1-YN-1-YL]PYRIMIDINE-2,4-DIAMINE (UCP1062)==		==Staphylococcus aureus Dihydrofolate Reductase complexed with NADPH and 6-ETHYL-5-[(3S)-3-[3-METHOXY-5-(PYRIDIN-4-YL)PHENYL]BUT-1-YN-1-YL]PYRIMIDINE-2,4-DIAMINE (UCP1062)==
	<StructureSection load='4tu5' size='340' side='right' caption='[[4tu5]], [[Resolution\|resolution]] 2.16Å' scene=''>		<StructureSection load='4tu5' size='340' side='right' caption='[[4tu5]], [[Resolution\|resolution]] 2.16Å' scene=''>
Line 6:		Line 7:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4tu2\|4tu2]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4tu2\|4tu2]]</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=4tu5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4tu5 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4tu5 RCSB], [http://www.ebi.ac.uk/pdbsum/4tu5 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=4tu5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4tu5 OCA], [http://pdbe.org/4tu5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4tu5 RCSB], [http://www.ebi.ac.uk/pdbsum/4tu5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4tu5 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 18:		Line 19:
	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 4tu5" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Dihydrofolate reductase\|Dihydrofolate reductase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 08:36, 29 July 2015

OCA — Wed, 29 Jul 2015 08:36:36 GMT

←Older revision		Revision as of 08:36, 29 July 2015
Line 10:		Line 10:
	== 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]		[[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]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	While antifolates such as Bactrim (trimethoprim-sulfamethoxazole; TMP-SMX) continue to play an important role in treating community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA), resistance-conferring mutations, specifically F98Y of dihydrofolate reductase (DHFR), have arisen and compromise continued use. In an attempt to extend the lifetime of this important class, we have developed a class of propargyl-linked antifolates (PLAs) that exhibit potent inhibition of the enzyme and bacterial strains. Probing the role of the configuration at the single propargylic stereocenter in these inhibitors required us to develop a new approach to nonracemic 3-aryl-1-butyne building blocks by the pairwise use of asymmetric conjugate addition and aldehyde dehydration protocols. Using this new route, a series of nonracemic PLA inhibitors was prepared and shown to possess potent enzyme inhibition (IC50 values <50 nM), antibacterial effects (several with MIC values <1 mug/mL) and to form stable ternary complexes with both wild-type and resistant mutants. Unexpectedly, crystal structures of a pair of individual enantiomers in the wild-type DHFR revealed that the single change in configuration of the stereocenter drove the selection of an alternative NADPH cofactor, with the minor alpha-anomer appearing with R-27. Remarkably, this cofactor switching becomes much more prevalent when the F98Y mutation is present. The observation of cofactor site plasticity leads to a postulate for the structural basis of TMP resistance in DHFR and also suggests design strategies that can be used to target these resistant enzymes.
		+
		+	Nonracemic Antifolates Stereoselectively Recruit Alternate Cofactors and Overcome Resistance in S. aureus.,Keshipeddy S, Reeve SM, Anderson AC, Wright DL J Am Chem Soc. 2015 Jul 8. PMID:26098608<ref>PMID:26098608</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 14:51, 8 July 2015

OCA — Wed, 08 Jul 2015 14:51:30 GMT

←Older revision		Revision as of 14:51, 8 July 2015
Line 1:		Line 1:
-	'''~~Unreleased structure~~'''	+	==Staphylococcus aureus Dihydrofolate Reductase complexed with NADPH and 6-ETHYL-5-[(3S)-3-[3-METHOXY-5-(PYRIDIN-4-YL)PHENYL]BUT-1-YN-1-YL]PYRIMIDINE-2,4-DIAMINE (UCP1062)==
-		+	<StructureSection load='4tu5' size='340' side='right' caption='[[4tu5]], [[Resolution\|resolution]] 2.16Å' scene=''>
-	~~The entry~~ 4tu5 is ~~ON HOLD until Paper Publication~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[4tu5]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4TU5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4TU5 FirstGlance]. <br>
-	~~Authors~~: ~~Reeve, S~~.M.~~, Anderson, A~~.C.	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=06W:6-ETHYL-5-{(3S)-3-[3-METHOXY-5-(PYRIDIN-4-YL)PHENYL]BUT-1-YN-1-YL}PYRIMIDINE-2,4-DIAMINE'>06W</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">[[4tu2\|4tu2]]</td></tr>
-	~~Description~~: ~~Staphylococcus aureus Dihydrofolate Reductase complexed with NADPH and~~ 6-ETHYL-5-[(3S)-3-[3-METHOXY-5-(PYRIDIN-4-YL)PHENYL]BUT-1-YN-1-YL]PYRIMIDINE-2,4-DIAMINE (~~UCP1062~~)	+	<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>
-	[[Category: ~~Unreleased Structures~~]]	+	<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=4tu5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4tu5 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4tu5 RCSB], [http://www.ebi.ac.uk/pdbsum/4tu5 PDBsum]</span></td></tr>
-	[[Category: Anderson, A.C]]	+	</table>
-	[[Category: Reeve, S.M]]	+	== 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]
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Dihydrofolate reductase]]
		+	[[Category: Anderson, A C]]
		+	[[Category: Reeve, S M]]
		+	[[Category: Antifolate]]
		+	[[Category: Enantiopure inhibitor]]
		+	[[Category: Methicillin-resistant staphylococcus aureus]]
		+	[[Category: Oxidoreductase]]
		+	[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]

OCA at 17:52, 24 December 2014

OCA — Wed, 24 Dec 2014 17:52:27 GMT

←Older revision		Revision as of 17:52, 24 December 2014
Line 6:		Line 6:

	Description: Staphylococcus aureus Dihydrofolate Reductase complexed with NADPH and 6-ETHYL-5-[(3S)-3-[3-METHOXY-5-(PYRIDIN-4-YL)PHENYL]BUT-1-YN-1-YL]PYRIMIDINE-2,4-DIAMINE (UCP1062)		Description: Staphylococcus aureus Dihydrofolate Reductase complexed with NADPH and 6-ETHYL-5-[(3S)-3-[3-METHOXY-5-(PYRIDIN-4-YL)PHENYL]BUT-1-YN-1-YL]PYRIMIDINE-2,4-DIAMINE (UCP1062)
		+	[[Category: Unreleased Structures]]
		+	[[Category: Anderson, A.C]]
		+	[[Category: Reeve, S.M]]

OCA at 08:40, 24 September 2014

OCA — Wed, 24 Sep 2014 08:40:17 GMT

←Older revision		Revision as of 08:40, 24 September 2014
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4tu5 is ON HOLD	+	The entry 4tu5 is ON HOLD until Paper Publication

	Authors: Reeve, S.M., Anderson, A.C.		Authors: Reeve, S.M., Anderson, A.C.

	Description: Staphylococcus aureus Dihydrofolate Reductase complexed with NADPH and 6-ETHYL-5-[(3S)-3-[3-METHOXY-5-(PYRIDIN-4-YL)PHENYL]BUT-1-YN-1-YL]PYRIMIDINE-2,4-DIAMINE (UCP1062)		Description: Staphylococcus aureus Dihydrofolate Reductase complexed with NADPH and 6-ETHYL-5-[(3S)-3-[3-METHOXY-5-(PYRIDIN-4-YL)PHENYL]BUT-1-YN-1-YL]PYRIMIDINE-2,4-DIAMINE (UCP1062)

OCA: Protected "4tu5" [edit=sysop:move=sysop]

OCA — Wed, 02 Jul 2014 07:34:13 GMT

Protected "4tu5" [edit=sysop:move=sysop]

←Older revision

Revision as of 07:34, 2 July 2014