4kak - Revision history

OCA at 15:56, 20 September 2023

OCA — Wed, 20 Sep 2023 15:56:31 GMT

←Older revision		Revision as of 15:56, 20 September 2023
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4kak]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4KAK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4KAK FirstGlance]. <br>		<table><tr><td colspan='2'>[[4kak]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4KAK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4KAK FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=06U:6-ETHYL-5-{(3R)-3-[3-METHOXY-5-(PYRIDIN-4-YL)PHENYL]BUT-1-YN-1-YL}PYRIMIDINE-2,4-DIAMINE'>06U</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=EOH:ETHANOL'>EOH</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]] 1.8Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=06U:6-ETHYL-5-{(3R)-3-[3-METHOXY-5-(PYRIDIN-4-YL)PHENYL]BUT-1-YN-1-YL}PYRIMIDINE-2,4-DIAMINE'>06U</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=EOH:ETHANOL'>EOH</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=4kak FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kak OCA], [https://pdbe.org/4kak PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4kak RCSB], [https://www.ebi.ac.uk/pdbsum/4kak PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4kak 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=4kak FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kak OCA], [https://pdbe.org/4kak PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4kak RCSB], [https://www.ebi.ac.uk/pdbsum/4kak PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4kak ProSAT]</span></td></tr>
	</table>		</table>

OCA at 11:48, 30 November 2022

OCA — Wed, 30 Nov 2022 11:48:53 GMT

←Older revision		Revision as of 11:48, 30 November 2022
Line 1:		Line 1:

	==Crystal structure of human dihydrofolate reductase complexed with NADPH and 6-ethyl-5-[(3S)-3-[3-methoxy-5-(pyridine-4-yl)phenyl]but-1-yn-1-yl]pyrimidine-2,4-diamine (UCP1006)==		==Crystal structure of human dihydrofolate reductase complexed with NADPH and 6-ethyl-5-[(3S)-3-[3-methoxy-5-(pyridine-4-yl)phenyl]but-1-yn-1-yl]pyrimidine-2,4-diamine (UCP1006)==
-	<StructureSection load='4kak' size='340' side='right' caption='[[4kak]], [[Resolution\|resolution]] 1.80Å' scene=''>	+	<StructureSection load='4kak' size='340' side='right'caption='[[4kak]], [[Resolution\|resolution]] 1.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4kak]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4KAK OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4KAK FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4kak]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4KAK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4KAK FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=06U:6-ETHYL-5-{(3R)-3-[3-METHOXY-5-(PYRIDIN-4-YL)PHENYL]BUT-1-YN-1-YL}PYRIMIDINE-2,4-DIAMINE'>06U</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=EOH:ETHANOL'>EOH</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=06U:6-ETHYL-5-{(3R)-3-[3-METHOXY-5-(PYRIDIN-4-YL)PHENYL]BUT-1-YN-1-YL}PYRIMIDINE-2,4-DIAMINE'>06U</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=EOH:ETHANOL'>EOH</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">[[4kbn\|4kbn]], [[4kd7\|4kd7]], [[4keb\|4keb]], [[4kfj\|4kfj]]</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=4kak FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kak OCA], [https://pdbe.org/4kak PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4kak RCSB], [https://www.ebi.ac.uk/pdbsum/4kak PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4kak ProSAT]</span></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">DHFR, huDHFR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4kak FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kak OCA], [~~http~~://pdbe.org/4kak PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4kak RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4kak PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4kak ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/DYR_HUMAN DYR_HUMAN]] Defects in DHFR are the cause of megaloblastic anemia due to dihydrofolate reductase deficiency (DHFRD) [MIM:[~~http~~://omim.org/entry/613839 613839]]. DHFRD is an inborn error of metabolism, characterized by megaloblastic anemia and/or pancytopenia, severe cerebral folate deficiency, and cerebral tetrahydrobiopterin deficiency. Clinical features include variable neurologic symptoms, ranging from severe developmental delay and generalized seizures in infancy, to childhood absence epilepsy with learning difficulties, to lack of symptoms.<ref>PMID:21310276</ref> <ref>PMID:21310277</ref>	+	[https://www.uniprot.org/uniprot/DYR_HUMAN DYR_HUMAN] Defects in DHFR are the cause of megaloblastic anemia due to dihydrofolate reductase deficiency (DHFRD) [MIM:[https://omim.org/entry/613839 613839]. DHFRD is an inborn error of metabolism, characterized by megaloblastic anemia and/or pancytopenia, severe cerebral folate deficiency, and cerebral tetrahydrobiopterin deficiency. Clinical features include variable neurologic symptoms, ranging from severe developmental delay and generalized seizures in infancy, to childhood absence epilepsy with learning difficulties, to lack of symptoms.<ref>PMID:21310276</ref> <ref>PMID:21310277</ref>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/DYR_HUMAN DYR_HUMAN]] Key enzyme in folate metabolism. Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis. Binds its own mRNA and that of DHFRL1.<ref>PMID:21876188</ref> <ref>PMID:12096917</ref>	+	[https://www.uniprot.org/uniprot/DYR_HUMAN DYR_HUMAN] Key enzyme in folate metabolism. Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis. Binds its own mRNA and that of DHFRL1.<ref>PMID:21876188</ref> <ref>PMID:12096917</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	==See Also==		==See Also==
-	*[[Dihydrofolate reductase\|Dihydrofolate reductase]]	+	*[[Dihydrofolate reductase 3D structures\|Dihydrofolate reductase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Dihydrofolate reductase~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Human~~]]	+	[[Category: Large Structures]]
-	[[Category: Anderson~~, A C~~]]	+	[[Category: Anderson AC]]
-	[[Category: Lamb~~, K M]]~~	+	[[Category: Lamb KM]]
-	~~[[Category: 8-dihydrofolate]]~~	+
-	~~[[Category: 8-tetrahydrofolate]]~~	+
-	~~[[Category: Hydride shift]]~~	+
-	~~[[Category: Nadp+]]~~	+
-	~~[[Category: Oxidoreductase]]~~	+
-	~~[[Category: Oxidoreductase-oxidoreductase inhibitor complex~~]]	+

OCA at 07:27, 23 December 2016

OCA — Fri, 23 Dec 2016 07:27:11 GMT

←Older revision		Revision as of 07:27, 23 December 2016
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		+
	==Crystal structure of human dihydrofolate reductase complexed with NADPH and 6-ethyl-5-[(3S)-3-[3-methoxy-5-(pyridine-4-yl)phenyl]but-1-yn-1-yl]pyrimidine-2,4-diamine (UCP1006)==		==Crystal structure of human dihydrofolate reductase complexed with NADPH and 6-ethyl-5-[(3S)-3-[3-methoxy-5-(pyridine-4-yl)phenyl]but-1-yn-1-yl]pyrimidine-2,4-diamine (UCP1006)==
	<StructureSection load='4kak' size='340' side='right' caption='[[4kak]], [[Resolution\|resolution]] 1.80Å' scene=''>		<StructureSection load='4kak' size='340' side='right' caption='[[4kak]], [[Resolution\|resolution]] 1.80Å' scene=''>
Line 7:		Line 8:
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">DHFR, huDHFR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">DHFR, huDHFR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4kak FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kak OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4kak RCSB], [http://www.ebi.ac.uk/pdbsum/4kak 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=4kak FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kak OCA], [http://pdbe.org/4kak PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4kak RCSB], [http://www.ebi.ac.uk/pdbsum/4kak PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4kak ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 21:		Line 22:
	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 4kak" style="background-color:#fffaf0;"></div>

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

OCA at 08:52, 15 February 2015

OCA — Sun, 15 Feb 2015 08:52:51 GMT

←Older revision		Revision as of 08:52, 15 February 2015
Line 1:		Line 1:
-	~~{{STRUCTURE_4kak\| PDB=4kak \| SCENE= }}~~	+	==Crystal structure of human dihydrofolate reductase complexed with NADPH and 6-ethyl-5-[(3S)-3-[3-methoxy-5-(pyridine-4-yl)phenyl]but-1-yn-1-yl]pyrimidine-2,4-diamine (UCP1006)==
-	===Crystal structure of human dihydrofolate reductase complexed with NADPH and 6-ethyl-5-[(3S)-3-[3-methoxy-5-(pyridine-4-yl)phenyl]but-1-yn-1-yl]pyrimidine-2,4-diamine (UCP1006)===	+	<StructureSection load='4kak' size='340' side='right' caption='[[4kak]], [[Resolution\|resolution]] 1.80Å' scene=''>
-	{~~{ABSTRACT_PUBMED_24053334}~~}	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[4kak]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4KAK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4KAK FirstGlance]. <br>
-	==Disease==	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=06U:6-ETHYL-5-{(3R)-3-[3-METHOXY-5-(PYRIDIN-4-YL)PHENYL]BUT-1-YN-1-YL}PYRIMIDINE-2,4-DIAMINE'>06U</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=EOH:ETHANOL'>EOH</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">[[4kbn\|4kbn]], [[4kd7\|4kd7]], [[4keb\|4keb]], [[4kfj\|4kfj]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">DHFR, huDHFR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4kak FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kak OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4kak RCSB], [http://www.ebi.ac.uk/pdbsum/4kak PDBsum]</span></td></tr>
		+	</table>
		+	== Disease ==
	[[http://www.uniprot.org/uniprot/DYR_HUMAN DYR_HUMAN]] Defects in DHFR are the cause of megaloblastic anemia due to dihydrofolate reductase deficiency (DHFRD) [MIM:[http://omim.org/entry/613839 613839]]. DHFRD is an inborn error of metabolism, characterized by megaloblastic anemia and/or pancytopenia, severe cerebral folate deficiency, and cerebral tetrahydrobiopterin deficiency. Clinical features include variable neurologic symptoms, ranging from severe developmental delay and generalized seizures in infancy, to childhood absence epilepsy with learning difficulties, to lack of symptoms.<ref>PMID:21310276</ref> <ref>PMID:21310277</ref>		[[http://www.uniprot.org/uniprot/DYR_HUMAN DYR_HUMAN]] Defects in DHFR are the cause of megaloblastic anemia due to dihydrofolate reductase deficiency (DHFRD) [MIM:[http://omim.org/entry/613839 613839]]. DHFRD is an inborn error of metabolism, characterized by megaloblastic anemia and/or pancytopenia, severe cerebral folate deficiency, and cerebral tetrahydrobiopterin deficiency. Clinical features include variable neurologic symptoms, ranging from severe developmental delay and generalized seizures in infancy, to childhood absence epilepsy with learning difficulties, to lack of symptoms.<ref>PMID:21310276</ref> <ref>PMID:21310277</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/DYR_HUMAN DYR_HUMAN]] Key enzyme in folate metabolism. Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis. Binds its own mRNA and that of DHFRL1.<ref>PMID:21876188</ref> <ref>PMID:12096917</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The pursuit of antimicrobial drugs that target dihydrofolate reductase (DHFR) exploits differences in sequence and dynamics between the pathogenic and human enzymes. Here, we present five crystal structures of human DHFR bound to a new class of antimicrobial agents, the propargyl-linked antifolates (PLAs), with a range of potency (IC50 values of 0.045-1.07 muM) for human DHFR. These structures reveal that interactions between the ligands and Asn 64, Phe 31, and Phe 34 are important for increased affinity for human DHFR and that loop residues 58-64 undergo ligand-induced conformational changes. The utility of these structural studies was demonstrated through the design of three new ligands that reduce the number of contacts with Asn 64, Phe 31, and Phe 34. Synthesis and evaluation show that one of the designed inhibitors exhibits the lowest affinity for human DHFR of any of the PLAs (2.64 muM). Comparisons of structures of human and Staphylococcus aureus DHFR bound to the same PLA reveal a conformational change in the ligand that enhances interactions with residues Phe 92 (Val 115 in huDHFR) and Ile 50 (Ile 60 in huDHFR) in S. aureus DHFR, yielding selectivity. Likewise, comparisons of human and Candida glabrata DHFR bound to the same ligand show that hydrophobic interactions with residues Ile 121 and Phe 66 (Val 115 and Asn 64 in human DHFR) yield selective inhibitors. The identification of residue substitutions that are important for selectivity and the observation of active site flexibility will help guide antimicrobial antifolate development for the inhibition of pathogenic species.

-	~~==Function==~~	+	Elucidating Features That Drive the Design of Selective Antifolates Using Crystal Structures of Human Dihydrofolate Reductase.,Lamb KM, G-Dayanandan N, Wright DL, Anderson AC Biochemistry. 2013 Oct 3. PMID:24053334<ref>PMID:24053334</ref>
-	~~[[http://www.uniprot.org/uniprot/DYR_HUMAN DYR_HUMAN]] Key enzyme in folate metabolism. Contributes to~~ the ~~de novo mitochondrial thymidylate biosynthesis pathway~~. ~~Catalyzes an essential reaction for de novo glycine and purine synthesis~~, ~~and for DNA precursor synthesis~~. ~~Binds its own mRNA and that of DHFRL1~~.~~<ref>~~PMID:~~21876188</ref>~~ <ref>PMID:~~12096917~~</ref>	+

-	~~==About this Structure==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[4kak]] is~~ a ~~2 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Human Human]~~. ~~Full crystallographic information is available from [http:~~/~~/oca.weizmann.ac.il/oca-bin/ocashort?id=4KAK OCA].~~	+	</div>

-	==~~Reference~~==	+	==See Also==
-	~~<ref group~~=~~"xtra">PMID:024053334</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	*[[Dihydrofolate reductase\|Dihydrofolate reductase]]
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Dihydrofolate reductase]]		[[Category: Dihydrofolate reductase]]
	[[Category: Human]]		[[Category: Human]]
-	[[Category: Anderson, A C.]]	+	[[Category: Anderson, A C]]
-	[[Category: Lamb, K M.]]	+	[[Category: Lamb, K M]]
	[[Category: 8-dihydrofolate]]		[[Category: 8-dihydrofolate]]
	[[Category: 8-tetrahydrofolate]]		[[Category: 8-tetrahydrofolate]]

OCA at 12:18, 20 November 2013

OCA — Wed, 20 Nov 2013 12:18:16 GMT

←Older revision		Revision as of 12:18, 20 November 2013
Line 10:		Line 10:

	==About this Structure==		==About this Structure==
-	[[4kak]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4KAK OCA].	+	[[4kak]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4KAK OCA].

	==Reference==		==Reference==
	<ref group="xtra">PMID:024053334</ref><references group="xtra"/><references/>		<ref group="xtra">PMID:024053334</ref><references group="xtra"/><references/>
	[[Category: Dihydrofolate reductase]]		[[Category: Dihydrofolate reductase]]
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Anderson, A C.]]		[[Category: Anderson, A C.]]
	[[Category: Lamb, K M.]]		[[Category: Lamb, K M.]]

OCA at 06:27, 10 October 2013

OCA — Thu, 10 Oct 2013 06:27:36 GMT

←Older revision		Revision as of 06:27, 10 October 2013
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-	~~'''Unreleased~~ structure~~'''~~	+	{{STRUCTURE_4kak\| PDB=4kak \| SCENE= }}
		+	===Crystal structure of human dihydrofolate reductase complexed with NADPH and 6-ethyl-5-[(3S)-3-[3-methoxy-5-(pyridine-4-yl)phenyl]but-1-yn-1-yl]pyrimidine-2,4-diamine (UCP1006)===
		+	{{ABSTRACT_PUBMED_24053334}}

-	~~The~~ entry ~~4kak~~ is ~~ON HOLD~~ ~~until Paper Publication~~	+	==Disease==
		+	[[http://www.uniprot.org/uniprot/DYR_HUMAN DYR_HUMAN]] Defects in DHFR are the cause of megaloblastic anemia due to dihydrofolate reductase deficiency (DHFRD) [MIM:[http://omim.org/entry/613839 613839]]. DHFRD is an inborn error of metabolism, characterized by megaloblastic anemia and/or pancytopenia, severe cerebral folate deficiency, and cerebral tetrahydrobiopterin deficiency. Clinical features include variable neurologic symptoms, ranging from severe developmental delay and generalized seizures in infancy, to childhood absence epilepsy with learning difficulties, to lack of symptoms.<ref>PMID:21310276</ref> <ref>PMID:21310277</ref>

-	~~Authors~~: ~~Lamb, K~~.M., ~~Anderson, A~~.C.	+	==Function==
		+	[[http://www.uniprot.org/uniprot/DYR_HUMAN DYR_HUMAN]] Key enzyme in folate metabolism. Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis. Binds its own mRNA and that of DHFRL1.<ref>PMID:21876188</ref> <ref>PMID:12096917</ref>

-	~~Description: Crystal~~ structure ~~of human dihydrofolate reductase complexed~~ with ~~NADPH and 6-ethyl-5-~~[~~(3S)-3~~-[~~3-methoxy~~-~~5-(pyridine-4-yl)phenyl~~]~~but-1-yn~~-~~1-yl~~]~~pyrimidine~~-~~2,4-diamine (UCP1006)~~	+	==About this Structure==
		+	[[4kak]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4KAK OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:024053334</ref><references group="xtra"/><references/>
		+	[[Category: Dihydrofolate reductase]]
		+	[[Category: Homo sapiens]]
		+	[[Category: Anderson, A C.]]
		+	[[Category: Lamb, K M.]]
		+	[[Category: 8-dihydrofolate]]
		+	[[Category: 8-tetrahydrofolate]]
		+	[[Category: Hydride shift]]
		+	[[Category: Nadp+]]
		+	[[Category: Oxidoreductase]]
		+	[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]

OCA at 04:09, 1 August 2013

OCA — Thu, 01 Aug 2013 04:09:52 GMT

←Older revision		Revision as of 04:09, 1 August 2013
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	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors: Lamb, K.M., Anderson, A.C.		Authors: Lamb, K.M., Anderson, A.C.

	Description: Crystal structure of human dihydrofolate reductase complexed with NADPH and 6-ethyl-5-[(3S)-3-[3-methoxy-5-(pyridine-4-yl)phenyl]but-1-yn-1-yl]pyrimidine-2,4-diamine (UCP1006)		Description: Crystal structure of human dihydrofolate reductase complexed with NADPH and 6-ethyl-5-[(3S)-3-[3-methoxy-5-(pyridine-4-yl)phenyl]but-1-yn-1-yl]pyrimidine-2,4-diamine (UCP1006)

OCA at 07:19, 8 May 2013

OCA — Wed, 08 May 2013 07:19:15 GMT

←Older revision		Revision as of 07:19, 8 May 2013
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	Authors: Lamb, K.M., Anderson, A.C.		Authors: Lamb, K.M., Anderson, A.C.

-	Description: Crystal structure of human dihydrofolate reductase complexed with NADPH and 6-ethyl-5-[(3R)-3-[3-methoxy-5-(pyridine-4-yl)phenyl]but-1-yn-1-yl]pyrimidine-2,4-diamine (UCP1006)	+	Description: Crystal structure of human dihydrofolate reductase complexed with NADPH and 6-ethyl-5-[(3S)-3-[3-methoxy-5-(pyridine-4-yl)phenyl]but-1-yn-1-yl]pyrimidine-2,4-diamine (UCP1006)

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

OCA — Thu, 02 May 2013 07:14:19 GMT

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

←Older revision

Revision as of 07:14, 2 May 2013

OCA: New page: '''Unreleased structure''' The entry 4kak is ON HOLD Authors: Lamb, K.M., Anderson, A.C. Description: Crystal structure of human dihydrofolate reductase complexed with NADPH and 6-ethy...

OCA — Thu, 02 May 2013 07:14:18 GMT

New page: '''Unreleased structure''' The entry 4kak is ON HOLD Authors: Lamb, K.M., Anderson, A.C. Description: Crystal structure of human dihydrofolate reductase complexed with NADPH and 6-ethy...

New page

'''Unreleased structure'''

The entry 4kak is ON HOLD

Authors: Lamb, K.M., Anderson, A.C.

Description: Crystal structure of human dihydrofolate reductase complexed with NADPH and 6-ethyl-5-[(3R)-3-[3-methoxy-5-(pyridine-4-yl)phenyl]but-1-yn-1-yl]pyrimidine-2,4-diamine (UCP1006)