6pfe - Revision history

OCA at 07:28, 11 October 2023

OCA — Wed, 11 Oct 2023 07:28:22 GMT

←Older revision		Revision as of 07:28, 11 October 2023
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	<StructureSection load='6pfe' size='340' side='right'caption='[[6pfe]], [[Resolution\|resolution]] 2.81Å' scene=''>		<StructureSection load='6pfe' size='340' side='right'caption='[[6pfe]], [[Resolution\|resolution]] 2.81Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6pfe]] is a 5 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Cryho Cryho~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PFE OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6PFE FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6pfe]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Cryptosporidium_hominis Cryptosporidium hominis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PFE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6PFE FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MTX:METHOTREXATE'>MTX</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=OEA:2-({4-[(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)methyl]benzene-1-carbonyl}amino)-4-methoxybenzoic+acid'>OEA</scene>, <scene name='pdbligand=UFP:5-FLUORO-2-DEOXYURIDINE-5-MONOPHOSPHATE'>UFP</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]] 2.812Å</td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CHUDEA4_4460 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=237895 CRYHO])~~</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MTX:METHOTREXATE'>MTX</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=OEA:2-({4-[(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)methyl]benzene-1-carbonyl}amino)-4-methoxybenzoic+acid'>OEA</scene>, <scene name='pdbligand=UFP:5-FLUORO-2-DEOXYURIDINE-5-MONOPHOSPHATE'>UFP</scene></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=6pfe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pfe OCA], [~~http~~://pdbe.org/6pfe PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6pfe RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6pfe PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6pfe 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=6pfe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pfe OCA], [https://pdbe.org/6pfe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6pfe RCSB], [https://www.ebi.ac.uk/pdbsum/6pfe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6pfe ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/A0A0S4TER9_CRYHO A0A0S4TER9_CRYHO]] Bifunctional enzyme. Involved in de novo dTMP biosynthesis. Key enzyme in folate metabolism.[PIRNR:PIRNR000389]	+	[https://www.uniprot.org/uniprot/A0A0S4TER9_CRYHO A0A0S4TER9_CRYHO] Bifunctional enzyme. Involved in de novo dTMP biosynthesis. Key enzyme in folate metabolism.[PIRNR:PIRNR000389]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</div>		</div>
	<div class="pdbe-citations 6pfe" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6pfe" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Dihydrofolate reductase 3D structures\|Dihydrofolate reductase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Cryho~~]]	+	[[Category: Cryptosporidium hominis]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Anderson~~, K S~~]]	+	[[Category: Anderson KS]]
-	[[Category: Czyzyk~~, D J~~]]	+	[[Category: Czyzyk DJ]]
-	[[Category: Jorgensen~~, W L~~]]	+	[[Category: Jorgensen WL]]
-	[[Category: Valhondo, M]]	+	[[Category: Valhondo M]]
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Transferase]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex]]~~	+
-	~~[[Category: Ts-dhfr~~]]	+

OCA at 12:25, 18 December 2019

OCA — Wed, 18 Dec 2019 12:25:03 GMT

←Older revision		Revision as of 12:25, 18 December 2019
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	<StructureSection load='6pfe' size='340' side='right'caption='[[6pfe]], [[Resolution\|resolution]] 2.81Å' scene=''>		<StructureSection load='6pfe' size='340' side='right'caption='[[6pfe]], [[Resolution\|resolution]] 2.81Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6pfe]] is a 5 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PFE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6PFE FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6pfe]] is a 5 chain structure with sequence from [http://en.wikipedia.org/wiki/Cryho Cryho]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PFE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6PFE FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MTX:METHOTREXATE'>MTX</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=OEA:2-({4-[(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)methyl]benzene-1-carbonyl}amino)-4-methoxybenzoic+acid'>OEA</scene>, <scene name='pdbligand=UFP:5-FLUORO-2-DEOXYURIDINE-5-MONOPHOSPHATE'>UFP</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MTX:METHOTREXATE'>MTX</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=OEA:2-({4-[(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)methyl]benzene-1-carbonyl}amino)-4-methoxybenzoic+acid'>OEA</scene>, <scene name='pdbligand=UFP:5-FLUORO-2-DEOXYURIDINE-5-MONOPHOSPHATE'>UFP</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CHUDEA4_4460 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=237895 CRYHO])</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=6pfe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pfe OCA], [http://pdbe.org/6pfe PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6pfe RCSB], [http://www.ebi.ac.uk/pdbsum/6pfe PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6pfe 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=6pfe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pfe OCA], [http://pdbe.org/6pfe PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6pfe RCSB], [http://www.ebi.ac.uk/pdbsum/6pfe PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6pfe ProSAT]</span></td></tr>
	</table>		</table>
Line 22:		Line 23:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Cryho]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Anderson, K S]]		[[Category: Anderson, K S]]

OCA at 10:30, 2 October 2019

OCA — Wed, 02 Oct 2019 10:30:45 GMT

←Older revision		Revision as of 10:30, 2 October 2019
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-	'''Unreleased structure'''

-	~~The entry~~ 6pfe is ~~ON HOLD until Paper~~ Publication	+	==Crystal structure of TS-DHFR from Cryptosporidium hominis in complex with NADPH, FdUMP and 2-(4-((2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)methyl)benzamido)-4-methoxybenzoic acid.==
		+	<StructureSection load='6pfe' size='340' side='right'caption='[[6pfe]], [[Resolution\|resolution]] 2.81Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6pfe]] is a 5 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PFE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6PFE FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MTX:METHOTREXATE'>MTX</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=OEA:2-({4-[(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)methyl]benzene-1-carbonyl}amino)-4-methoxybenzoic+acid'>OEA</scene>, <scene name='pdbligand=UFP:5-FLUORO-2-DEOXYURIDINE-5-MONOPHOSPHATE'>UFP</scene></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=6pfe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pfe OCA], [http://pdbe.org/6pfe PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6pfe RCSB], [http://www.ebi.ac.uk/pdbsum/6pfe PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6pfe ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/A0A0S4TER9_CRYHO A0A0S4TER9_CRYHO]] Bifunctional enzyme. Involved in de novo dTMP biosynthesis. Key enzyme in folate metabolism.[PIRNR:PIRNR000389]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Cryptosporidiosis is a human gastrointestinal disease caused by protozoans of the genus Cryptosporidium, which can be fatal in immunocompromised individuals. The essential enzyme, thymidylate synthase (TS), is responsible for de novo synthesis of deoxythymidine monophosphate. The TS active site is relatively conserved between Cryptosporidium and human enzymes. In previous work, we identified compound 1, (2-amino-4-oxo-4,7-dihydro-pyrrolo[2,3-d]pyrimidin-methyl-phenyl-l-glutamic acid), as a promising selective Cryptosporidium hominis TS (ChTS) inhibitor. In the present study, we explore the structure-activity relationship around 1 glutamate moiety by synthesizing and biochemically evaluating the inhibitory activity of analogues against ChTS and human TS (hTS). X-Ray crystal structures were obtained for compounds bound to both ChTS and hTS. We establish the importance of the 2-phenylacetic acid moiety methylene linker in optimally positioning compounds 23, 24, and 25 within the active site. Moreover, through the comparison of structural data for 5, 14, 15, and 23 bound in both ChTS and hTS identified that active site rigidity is a driving force in determining inhibitor selectivity.

-	~~Authors: Czyzyk, D.J~~., ~~Valhondo~~, M., Jorgensen, W.L.~~, Anderson, K~~.S.	+	Structure activity relationship towards design of cryptosporidium specific thymidylate synthase inhibitors.,Czyzyk DJ, Valhondo M, Deiana L, Tirado-Rives J, Jorgensen WL, Anderson KS Eur J Med Chem. 2019 Sep 4;183:111673. doi: 10.1016/j.ejmech.2019.111673. PMID:31536894<ref>PMID:31536894</ref>

-	~~Description: Crystal structure~~ of TS-~~DHFR from Cryptosporidium hominis in complex with NADPH, FdUMP and 2~~-~~(4-((2-amino-4-oxo-4~~,~~7-dihydro-3H-pyrrolo~~[2,~~3-d~~]~~pyrimidin-5-yl)methyl)benzamido)-4-methoxybenzoic acid.~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 6pfe" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Anderson, K S]]
		+	[[Category: Czyzyk, D J]]
		+	[[Category: Jorgensen, W L]]
	[[Category: Valhondo, M]]		[[Category: Valhondo, M]]
-	[[Category: ~~Czyzyk, D.J~~]]	+	[[Category: Inhibitor]]
-	[[Category: ~~Anderson, K.S~~]]	+	[[Category: Transferase]]
-	[[Category: ~~Jorgensen, W.L~~]]	+	[[Category: Transferase-transferase inhibitor complex]]
		+	[[Category: Ts-dhfr]]

OCA: Protected "6pfe" [edit=sysop:move=sysop]

OCA — Wed, 03 Jul 2019 04:15:39 GMT

Protected "6pfe" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:15, 3 July 2019

OCA: New page: '''Unreleased structure''' The entry 6pfe is ON HOLD until Paper Publication Authors: Czyzyk, D.J., Valhondo, M., Jorgensen, W.L., Anderson, K.S. Description: Crystal structure of TS-D...

OCA — Wed, 03 Jul 2019 04:15:37 GMT

New page: '''Unreleased structure''' The entry 6pfe is ON HOLD until Paper Publication Authors: Czyzyk, D.J., Valhondo, M., Jorgensen, W.L., Anderson, K.S. Description: Crystal structure of TS-D...

New page

'''Unreleased structure'''

The entry 6pfe is ON HOLD until Paper Publication

Authors: Czyzyk, D.J., Valhondo, M., Jorgensen, W.L., Anderson, K.S.

Description: Crystal structure of TS-DHFR from Cryptosporidium hominis in complex with NADPH, FdUMP and 2-(4-((2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)methyl)benzamido)-4-methoxybenzoic acid.
[[Category: Unreleased Structures]]
[[Category: Valhondo, M]]
[[Category: Czyzyk, D.J]]
[[Category: Anderson, K.S]]
[[Category: Jorgensen, W.L]]