3s7a - Revision history

OCA at 12:48, 14 March 2024

OCA — Thu, 14 Mar 2024 12:48:55 GMT

←Older revision		Revision as of 12:48, 14 March 2024
Line 3:		Line 3:
	<StructureSection load='3s7a' size='340' side='right'caption='[[3s7a]], [[Resolution\|resolution]] 1.80Å' scene=''>		<StructureSection load='3s7a' size='340' side='right'caption='[[3s7a]], [[Resolution\|resolution]] 1.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3s7a]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3S7A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3S7A FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3s7a]] is a 1 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=3S7A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3S7A FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=684:4-({5-[(2,4-DIAMINOPTERIDIN-6-YL)METHYL]-5H-DIBENZO[B,F]AZEPIN-2-YL}OXY)BUTANOIC+ACID'>684</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">DHFR ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=684:4-({5-[(2,4-DIAMINOPTERIDIN-6-YL)METHYL]-5H-DIBENZO[B,F]AZEPIN-2-YL}OXY)BUTANOIC+ACID'>684</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Dihydrofolate_reductase Dihydrofolate reductase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.3 1.5.1.3] </span></td></tr>	+
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3s7a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3s7a OCA], [https://pdbe.org/3s7a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3s7a RCSB], [https://www.ebi.ac.uk/pdbsum/3s7a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3s7a 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=3s7a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3s7a OCA], [https://pdbe.org/3s7a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3s7a RCSB], [https://www.ebi.ac.uk/pdbsum/3s7a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3s7a ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[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>	+	[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 ==
-	[[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>	+	[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;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	In order to understand the structure-activity profile observed for a series of substituted dibenz[b,f]azepine antifolates, the crystal structure of the binary complex of human dihydrofolate reductase (hDHFR) with the potent and selective inhibitor 2,4-diamino-6-{2'-O-(3-carboxypropyl)oxydibenz[b,f]-azepin-5-yl}methylpter idine (PT684) was determined to 1.8 A resolution. These data revealed that the carboxylate side chain of PT684 occupies two alternate positions, neither of which interacts with the conserved Arg70 in the active-site pocket, which in turn hydrogen bonds to water. These observations are in contrast to those reported for the ternary complex of mouse DHFR (mDHFR) with NADPH [Cody et al. (2008), Acta Cryst. D64, 977-984], in which the 3-carboxypropyl side chain of PT684 was hydrolyzed to its hydroxyl derivative, PT684a. The crystallization conditions differed for the human and mouse DHFR crystals (100 mM K(2)HPO(4) pH 6.9, 30% ammonium sulfate for hDHFR; 15 mM Tris pH 8.3, 75 mM sodium cacodylate, PEG 4K for mDHFR). Additionally, the side chains of Phe31 and Gln35 in the hDHFR complex have a single conformation, whereas in the mDHFR complex they occupied two alternative conformations. These data show that the hDHFR complex has a decreased active-site volume compared with the mDHFR complex, as reflected in a relative shift of helix C (residues 59-64) of 1.2 A, and a shift of 1.5 A compared with the ternary complex of Pneumocystis carinii DHFR (pcDHFR) with the parent dibenz[b,f]azepine PT653. These data suggest that the greater inhibitory potency of PT684 against pcDHFR is consistent with the larger active-site volume of pcDHFR and the predicted interactions of the carboxylate side chain with Arg75.	+
-		+
-	Structural analysis of human dihydrofolate reductase as a binary complex with the potent and selective inhibitor 2,4-diamino-6-{2'-O-(3-carboxypropyl)oxydibenz[b,f]-azepin-5-yl}methylpter idine reveals an unusual binding mode.,Cody V, Pace J, Nowak J Acta Crystallogr D Biol Crystallogr. 2011 Oct;67(Pt 10):875-80. Epub 2011, Sep 8. PMID:21931219<ref>PMID:21931219</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 3s7a" style="background-color:#fffaf0;"></div~~>	+

	==See Also==		==See Also==
Line 29:		Line 19:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Dihydrofolate reductase]]~~	+	[[Category: Homo sapiens]]
-	~~[[Category: Human~~]]	+
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Cody, V]]	+	[[Category: Cody V]]
-	[[Category: Nowak, J]]	+	[[Category: Nowak J]]
-	[[Category: Pace, J]]	+	[[Category: Pace J]]
-	~~[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]~~	+
-	~~[[Category: Reductase]]~~	+
-	~~[[Category: Single polypeptide chain~~]]	+

OCA at 10:41, 22 June 2022

OCA — Wed, 22 Jun 2022 10:41:10 GMT

←Older revision		Revision as of 10:41, 22 June 2022
Line 1:		Line 1:

	==Human dihydrofolate reductase binary complex with PT684==		==Human dihydrofolate reductase binary complex with PT684==
-	<StructureSection load='3s7a' size='340' side='right' caption='[[3s7a]], [[Resolution\|resolution]] 1.80Å' scene=''>	+	<StructureSection load='3s7a' size='340' side='right'caption='[[3s7a]], [[Resolution\|resolution]] 1.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3s7a]] is a 1 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=3S7A OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3S7A FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3s7a]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3S7A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3S7A FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=684:4-({5-[(2,4-DIAMINOPTERIDIN-6-YL)METHYL]-5H-DIBENZO[B,F]AZEPIN-2-YL}OXY)BUTANOIC+ACID'>684</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=684:4-({5-[(2,4-DIAMINOPTERIDIN-6-YL)METHYL]-5H-DIBENZO[B,F]AZEPIN-2-YL}OXY)BUTANOIC+ACID'>684</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">DHFR ([~~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 ([https://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'>[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=3s7a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3s7a OCA], [~~http~~://pdbe.org/3s7a PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3s7a RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3s7a PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3s7a 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=3s7a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3s7a OCA], [https://pdbe.org/3s7a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3s7a RCSB], [https://www.ebi.ac.uk/pdbsum/3s7a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3s7a 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 ==
Line 24:		Line 24:

	==See Also==		==See Also==
-	*[[Dihydrofolate reductase\|Dihydrofolate reductase]]	+	*[[Dihydrofolate reductase 3D structures\|Dihydrofolate reductase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 31:		Line 31:
	[[Category: Dihydrofolate reductase]]		[[Category: Dihydrofolate reductase]]
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Cody, V]]		[[Category: Cody, V]]
	[[Category: Nowak, J]]		[[Category: Nowak, J]]

OCA at 10:08, 5 August 2016

OCA — Fri, 05 Aug 2016 10:08:15 GMT

←Older revision		Revision as of 10:08, 5 August 2016
Line 1:		Line 1:
		+
	==Human dihydrofolate reductase binary complex with PT684==		==Human dihydrofolate reductase binary complex with PT684==
	<StructureSection load='3s7a' size='340' side='right' caption='[[3s7a]], [[Resolution\|resolution]] 1.80Å' scene=''>		<StructureSection load='3s7a' size='340' side='right' caption='[[3s7a]], [[Resolution\|resolution]] 1.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3s7a]] is a 1 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=3S7A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3S7A FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3s7a]] is a 1 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=3S7A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3S7A FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=684:4-({5-[(2,4-DIAMINOPTERIDIN-6-YL)METHYL]-5H-DIBENZO[B,F]AZEPIN-2-YL}OXY)BUTANOIC+ACID'>684</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=684:4-({5-[(2,4-DIAMINOPTERIDIN-6-YL)METHYL]-5H-DIBENZO[B,F]AZEPIN-2-YL}OXY)BUTANOIC+ACID'>684</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">DHFR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">DHFR ([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=3s7a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3s7a OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3s7a RCSB], [http://www.ebi.ac.uk/pdbsum/3s7a 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=3s7a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3s7a OCA], [http://pdbe.org/3s7a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3s7a RCSB], [http://www.ebi.ac.uk/pdbsum/3s7a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3s7a ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 20:		Line 21:
	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 3s7a" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 28:		Line 30:
	</StructureSection>		</StructureSection>
	[[Category: Dihydrofolate reductase]]		[[Category: Dihydrofolate reductase]]
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Cody, V]]		[[Category: Cody, V]]
	[[Category: Nowak, J]]		[[Category: Nowak, J]]

OCA at 07:20, 21 December 2014

OCA — Sun, 21 Dec 2014 07:20:31 GMT

←Older revision		Revision as of 07:20, 21 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_3s7a~~\| ~~PDB~~=3s7a \| ~~SCENE~~= }}	+	==Human dihydrofolate reductase binary complex with PT684==
-	===~~Human~~ dihydrofolate reductase ~~binary complex~~ with ~~PT684~~===	+	<StructureSection load='3s7a' size='340' side='right' caption='[[3s7a]], [[Resolution\|resolution]] 1.80Å' scene=''>
-	{~~{ABSTRACT_PUBMED_21931219}~~}	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3s7a]] is a 1 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=3S7A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3S7A FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=684:4-({5-[(2,4-DIAMINOPTERIDIN-6-YL)METHYL]-5H-DIBENZO[B,F]AZEPIN-2-YL}OXY)BUTANOIC+ACID'>684</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">DHFR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=3s7a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3s7a OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3s7a RCSB], [http://www.ebi.ac.uk/pdbsum/3s7a 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>
		+	== 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 ==
		+	In order to understand the structure-activity profile observed for a series of substituted dibenz[b,f]azepine antifolates, the crystal structure of the binary complex of human dihydrofolate reductase (hDHFR) with the potent and selective inhibitor 2,4-diamino-6-{2'-O-(3-carboxypropyl)oxydibenz[b,f]-azepin-5-yl}methylpter idine (PT684) was determined to 1.8 A resolution. These data revealed that the carboxylate side chain of PT684 occupies two alternate positions, neither of which interacts with the conserved Arg70 in the active-site pocket, which in turn hydrogen bonds to water. These observations are in contrast to those reported for the ternary complex of mouse DHFR (mDHFR) with NADPH [Cody et al. (2008), Acta Cryst. D64, 977-984], in which the 3-carboxypropyl side chain of PT684 was hydrolyzed to its hydroxyl derivative, PT684a. The crystallization conditions differed for the human and mouse DHFR crystals (100 mM K(2)HPO(4) pH 6.9, 30% ammonium sulfate for hDHFR; 15 mM Tris pH 8.3, 75 mM sodium cacodylate, PEG 4K for mDHFR). Additionally, the side chains of Phe31 and Gln35 in the hDHFR complex have a single conformation, whereas in the mDHFR complex they occupied two alternative conformations. These data show that the hDHFR complex has a decreased active-site volume compared with the mDHFR complex, as reflected in a relative shift of helix C (residues 59-64) of 1.2 A, and a shift of 1.5 A compared with the ternary complex of Pneumocystis carinii DHFR (pcDHFR) with the parent dibenz[b,f]azepine PT653. These data suggest that the greater inhibitory potency of PT684 against pcDHFR is consistent with the larger active-site volume of pcDHFR and the predicted interactions of the carboxylate side chain with Arg75.

-	~~==Disease==~~	+	Structural analysis of human dihydrofolate reductase as a binary complex with the potent and selective inhibitor 2,4-diamino-6-{2'-O-(3-carboxypropyl)oxydibenz[b,f]-azepin-5-yl}methylpter idine reveals an unusual binding mode.,Cody V, Pace J, Nowak J Acta Crystallogr D Biol Crystallogr. 2011 Oct;67(Pt 10):875-80. Epub 2011, Sep 8. PMID:21931219<ref>PMID:21931219</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==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[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>
-		+
-	~~==About this Structure==~~	+
-	[[3s7a]] is a 1 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=3S7A OCA].	+

	==See Also==		==See Also==
	*[[Dihydrofolate reductase\|Dihydrofolate reductase]]		*[[Dihydrofolate reductase\|Dihydrofolate reductase]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	~~<ref group="xtra">PMID:021931219</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Dihydrofolate reductase]]		[[Category: Dihydrofolate reductase]]
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Cody, V.]]	+	[[Category: Cody, V]]
-	[[Category: Nowak, J.]]	+	[[Category: Nowak, J]]
-	[[Category: Pace, J.]]	+	[[Category: Pace, J]]
	[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]		[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]
	[[Category: Reductase]]		[[Category: Reductase]]
	[[Category: Single polypeptide chain]]		[[Category: Single polypeptide chain]]

OCA at 20:07, 24 March 2013

OCA — Sun, 24 Mar 2013 20:07:11 GMT

←Older revision		Revision as of 20:07, 24 March 2013
Line 1:		Line 1:
-	[[Image:3s7a.png\|left\|200px]]
-
	{{STRUCTURE_3s7a\| PDB=3s7a \| SCENE= }}		{{STRUCTURE_3s7a\| PDB=3s7a \| SCENE= }}
-
	===Human dihydrofolate reductase binary complex with PT684===		===Human dihydrofolate reductase binary complex with PT684===
		+	{{ABSTRACT_PUBMED_21931219}}

-	~~{{ABSTRACT_PUBMED_21931219}}~~	+	==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>
		+
		+	==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>

	==About this Structure==		==About this Structure==
Line 14:		Line 16:

	==Reference==		==Reference==
-	<ref group="xtra">PMID:021931219</ref><references group="xtra"/>	+	<ref group="xtra">PMID:021931219</ref><references group="xtra"/><references/>
	[[Category: Dihydrofolate reductase]]		[[Category: Dihydrofolate reductase]]
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]

OCA at 11:08, 20 October 2012

OCA — Sat, 20 Oct 2012 11:08:21 GMT

←Older revision		Revision as of 11:08, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
-	[[3s7a]] is a 1 chain structure ~~of [[Dihydrofolate reductase]]~~ 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=3S7A OCA].	+	[[3s7a]] is a 1 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=3S7A OCA].

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

OCA at 04:21, 26 July 2012

OCA — Thu, 26 Jul 2012 04:21:46 GMT

←Older revision		Revision as of 04:21, 26 July 2012
Line 1:		Line 1:
-	[[Image:3s7a.~~jpg~~\|left\|200px]]	+	[[Image:3s7a.png\|left\|200px]]

-	<!--
-	The line below this paragraph, containing "STRUCTURE_3s7a", 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_3s7a\| PDB=3s7a \| SCENE= }}		{{STRUCTURE_3s7a\| PDB=3s7a \| SCENE= }}

	===Human dihydrofolate reductase binary complex with PT684===		===Human dihydrofolate reductase binary complex with PT684===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_21931219}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 21931219 is the PubMed ID number.
-	-->
	{{ABSTRACT_PUBMED_21931219}}		{{ABSTRACT_PUBMED_21931219}}

	==About this Structure==		==About this Structure==
-	[[3s7a]] is a 1 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=3S7A OCA].	+	[[3s7a]] is a 1 chain structure of [[Dihydrofolate reductase]] 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=3S7A OCA].
		+
		+	==See Also==
		+	*[[Dihydrofolate reductase\|Dihydrofolate reductase]]

	==Reference==		==Reference==

OCA at 06:40, 5 October 2011

OCA — Wed, 05 Oct 2011 06:40:30 GMT

←Older revision		Revision as of 06:40, 5 October 2011
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	[[Image:3s7a.jpg\|left\|200px]]

-	The ~~entry 3s7a~~ is ~~ON HOLD~~ ~~until Paper Publication~~	+	<!--
		+	The line below this paragraph, containing "STRUCTURE_3s7a", 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_3s7a\| PDB=3s7a \| SCENE= }}

-	~~Authors: Cody, V., Pace, J., Nowak, J.~~	+	===Human dihydrofolate reductase binary complex with PT684===

-	~~Description~~: ~~Human dihydrofolate~~ reductase ~~binary~~ complex ~~with PT684~~	+
		+	<!--
		+	The line below this paragraph, {{ABSTRACT_PUBMED_21931219}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 21931219 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_21931219}}
		+
		+	==About this Structure==
		+	[[3s7a]] is a 1 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=3S7A OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:021931219</ref><references group="xtra"/>
		+	[[Category: Dihydrofolate reductase]]
		+	[[Category: Homo sapiens]]
		+	[[Category: Cody, V.]]
		+	[[Category: Nowak, J.]]
		+	[[Category: Pace, J.]]
		+	[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]
		+	[[Category: Reductase]]
		+	[[Category: Single polypeptide chain]]

OCA at 05:55, 15 June 2011

OCA — Wed, 15 Jun 2011 05:55:20 GMT

←Older revision		Revision as of 05:55, 15 June 2011
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 3s7a is ON HOLD	+	The entry 3s7a is ON HOLD until Paper Publication

	Authors: Cody, V., Pace, J., Nowak, J.		Authors: Cody, V., Pace, J., Nowak, J.

	Description: Human dihydrofolate reductase binary complex with PT684		Description: Human dihydrofolate reductase binary complex with PT684

OCA at 04:53, 8 June 2011

OCA — Wed, 08 Jun 2011 04:53:58 GMT

←Older revision		Revision as of 04:53, 8 June 2011
Line 3:		Line 3:
	The entry 3s7a is ON HOLD		The entry 3s7a is ON HOLD

-	Authors: Cody, V., Pace, J, Nowak, J	+	Authors: Cody, V., Pace, J., Nowak, J.

-	Description: ~~human~~ dihydrofolate reductase binary complex with PT684	+	Description: Human dihydrofolate reductase binary complex with PT684