5ei3 - Revision history

OCA at 06:29, 5 July 2023

OCA — Wed, 05 Jul 2023 06:29:06 GMT

←Older revision		Revision as of 06:29, 5 July 2023
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	==Co-crystal structure of eIF4E with nucleotide mimetic inhibitor.==		==Co-crystal structure of eIF4E with nucleotide mimetic inhibitor.==
-	<StructureSection load='5ei3' size='340' side='right' caption='[[5ei3]], [[Resolution\|resolution]] 1.71Å' scene=''>	+	<StructureSection load='5ei3' size='340' side='right'caption='[[5ei3]], [[Resolution\|resolution]] 1.71Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5ei3]] 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=5EI3 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5EI3 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5ei3]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EI3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5EI3 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5O8:~{N}-[[(2~{R},3~{S},4~{R},5~{R})-5-[2-AZANYL-6-OXIDANYLIDENE-7-(PHENYLMETHYL)-1~{H}-PURIN-7-IUM-9-YL]-3,4-BIS(OXIDANYL)OXOLAN-2-YL]METHYL]-1,1,1-TRIS(FLUORANYL)METHANESULFONAMIDE'>5O8</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]] 1.71Å</td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2v8w\|2v8w]], [[5ehc\|5ehc]]</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5O8:~{N}-[[(2~{R},3~{S},4~{R},5~{R})-5-[2-AZANYL-6-OXIDANYLIDENE-7-(PHENYLMETHYL)-1~{H}-PURIN-7-IUM-9-YL]-3,4-BIS(OXIDANYL)OXOLAN-2-YL]METHYL]-1,1,1-TRIS(FLUORANYL)METHANESULFONAMIDE'>5O8</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">EIF4E, EIF4EL1, EIF4F ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])~~</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=5ei3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ei3 OCA], [https://pdbe.org/5ei3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ei3 RCSB], [https://www.ebi.ac.uk/pdbsum/5ei3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ei3 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=5ei3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ei3 OCA], [~~http~~://pdbe.org/5ei3 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5ei3 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5ei3 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5ei3 ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/IF4E_HUMAN IF4E_HUMAN]] Its translation stimulation activity is repressed by binding to the complex CYFIP1-FMR1 (By similarity). Recognizes and binds the 7-methylguanosine-containing mRNA cap during an early step in the initiation of protein synthesis and facilitates ribosome binding by inducing the unwinding of the mRNAs secondary structures. Component of the CYFIP1-EIF4E-FMR1 complex which binds to the mRNA cap and mediates translational repression. In the CYFIP1-EIF4E-FMR1 complex this subunit mediates the binding to the mRNA cap.<ref>PMID:16271312</ref>	+	[https://www.uniprot.org/uniprot/IF4E_HUMAN IF4E_HUMAN] Its translation stimulation activity is repressed by binding to the complex CYFIP1-FMR1 (By similarity). Recognizes and binds the 7-methylguanosine-containing mRNA cap during an early step in the initiation of protein synthesis and facilitates ribosome binding by inducing the unwinding of the mRNAs secondary structures. Component of the CYFIP1-EIF4E-FMR1 complex which binds to the mRNA cap and mediates translational repression. In the CYFIP1-EIF4E-FMR1 complex this subunit mediates the binding to the mRNA cap.<ref>PMID:16271312</ref>
	<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 5ei3" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5ei3" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Eukaryotic initiation factor 3D structures\|Eukaryotic initiation factor 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Fischer, P M~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Nowicki, M W~~]]	+	[[Category: Synthetic construct]]
-	[[Category: ~~Walkinshaw, M D~~]]	+	[[Category: Fischer PM]]
-	[[Category: ~~Complex~~]]	+	[[Category: Nowicki MW]]
-	[[Category: ~~Eif4e]]~~	+	[[Category: Walkinshaw MD]]
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Translation~~]]	+

OCA at 07:23, 29 November 2017

OCA — Wed, 29 Nov 2017 07:23:07 GMT

←Older revision		Revision as of 07:23, 29 November 2017
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	<StructureSection load='5ei3' size='340' side='right' caption='[[5ei3]], [[Resolution\|resolution]] 1.71Å' scene=''>		<StructureSection load='5ei3' size='340' side='right' caption='[[5ei3]], [[Resolution\|resolution]] 1.71Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5ei3]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EI3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5EI3 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5ei3]] 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=5EI3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5EI3 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5O8:~{N}-[[(2~{R},3~{S},4~{R},5~{R})-5-[2-AZANYL-6-OXIDANYLIDENE-7-(PHENYLMETHYL)-1~{H}-PURIN-7-IUM-9-YL]-3,4-BIS(OXIDANYL)OXOLAN-2-YL]METHYL]-1,1,1-TRIS(FLUORANYL)METHANESULFONAMIDE'>5O8</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=5O8:~{N}-[[(2~{R},3~{S},4~{R},5~{R})-5-[2-AZANYL-6-OXIDANYLIDENE-7-(PHENYLMETHYL)-1~{H}-PURIN-7-IUM-9-YL]-3,4-BIS(OXIDANYL)OXOLAN-2-YL]METHYL]-1,1,1-TRIS(FLUORANYL)METHANESULFONAMIDE'>5O8</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2v8w\|2v8w]], [[5ehc\|5ehc]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">EIF4E, EIF4EL1, EIF4F ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5ei3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ei3 OCA], [http://pdbe.org/5ei3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ei3 RCSB], [http://www.ebi.ac.uk/pdbsum/5ei3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ei3 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=5ei3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ei3 OCA], [http://pdbe.org/5ei3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ei3 RCSB], [http://www.ebi.ac.uk/pdbsum/5ei3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ei3 ProSAT]</span></td></tr>
	</table>		</table>
Line 22:		Line 24:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Fischer, P M]]		[[Category: Fischer, P M]]
	[[Category: Nowicki, M W]]		[[Category: Nowicki, M W]]

OCA at 08:12, 14 September 2016

OCA — Wed, 14 Sep 2016 08:12:50 GMT

←Older revision		Revision as of 08:12, 14 September 2016
Line 9:		Line 9:
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/IF4E_HUMAN IF4E_HUMAN]] Its translation stimulation activity is repressed by binding to the complex CYFIP1-FMR1 (By similarity). Recognizes and binds the 7-methylguanosine-containing mRNA cap during an early step in the initiation of protein synthesis and facilitates ribosome binding by inducing the unwinding of the mRNAs secondary structures. Component of the CYFIP1-EIF4E-FMR1 complex which binds to the mRNA cap and mediates translational repression. In the CYFIP1-EIF4E-FMR1 complex this subunit mediates the binding to the mRNA cap.<ref>PMID:16271312</ref>		[[http://www.uniprot.org/uniprot/IF4E_HUMAN IF4E_HUMAN]] Its translation stimulation activity is repressed by binding to the complex CYFIP1-FMR1 (By similarity). Recognizes and binds the 7-methylguanosine-containing mRNA cap during an early step in the initiation of protein synthesis and facilitates ribosome binding by inducing the unwinding of the mRNAs secondary structures. Component of the CYFIP1-EIF4E-FMR1 complex which binds to the mRNA cap and mediates translational repression. In the CYFIP1-EIF4E-FMR1 complex this subunit mediates the binding to the mRNA cap.<ref>PMID:16271312</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Eukaryotic translation initiation factor 4E (eIF4E) is considered as the corner stone in the cap-dependent translation initiation machinery. Its role is to recruit mRNA to the ribosome through recognition of the 5'-terminal mRNA cap structure (m7GpppN, where G is guanosine, N is any nucleotide). eIF4E is implicated in cell transformation, tumourigenesis, and angiogenesis by facilitating translation of oncogenic mRNAs; it is thus regarded as an attractive anticancer drug target. We have used two approaches to design cap-binding inhibitors of eIF4E by modifying the N7-substituent of m7GMP and replacing the phosphate group with isosteres such as squaramides, sulfonamides, and tetrazoles, as well as by structure-based virtual screening aimed at identifying non-nucleotide cap-binding antagonists. Phosphomimetic nucleotide derivatives and highly ranking virtual hits were evaluated in a series of in vitro and cell-based assays to identify the first non-nucleotide eIF4E cap-binding inhibitor with activities in cell-based assays, N-[(5,6-dihydro-6-oxo-1,3-dioxolo[4,5-g]quinolin-7-yl)methyl]-N'-(2-methyl-propyl )-N-(phenyl-methyl)thiourea (14), including down-regulation of oncogenic proteins and suppression of RNA incorporation into polysomes. Although we did not observe cellular activity with any of our modified m7GMP phosphate isostere compounds, we obtained X-ray crystallography structures of three such compounds in complex with eIF4E, 5'-deoxy-5'-(1,2-dioxo-3-hydroxycyclobut-3-en-4-yl)amino-N7-methyl-guanosine (4a), N7-3-chlorobenzyl-5'-deoxy-5'-(1,2-dioxo-3-hydroxy-cyclobut-3-en-4-yl)amino-guano sine (4f), and N7-benzyl-5'-deoxy-5'-(trifluoromethyl-sulfamoyl)guanosine (7a). Collectively, the data we present on structure-based design of eIF4E cap-binding inhibitors should facilitate the optimisation of such compounds as potential anticancer agents.
		+
		+	Design of nucleotide-mimetic and non-nucleotide inhibitors of the translation initiation factor eIF4E: Synthesis, structural and functional characterisation.,Soukarieh F, Nowicki MW, Bastide A, Poyry T, Jones C, Dudek K, Patwardhan G, Meullenet F, Oldham NJ, Walkinshaw MD, Willis AE, Fischer PM Eur J Med Chem. 2016 Aug 24;124:200-217. doi: 10.1016/j.ejmech.2016.08.047. PMID:27592390<ref>PMID:27592390</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 5ei3" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 21:03, 10 September 2016

OCA — Sat, 10 Sep 2016 21:03:58 GMT

←Older revision		Revision as of 21:03, 10 September 2016
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5ei3 is ~~ON HOLD until Paper Publication~~	+	==Co-crystal structure of eIF4E with nucleotide mimetic inhibitor.==
-		+	<StructureSection load='5ei3' size='340' side='right' caption='[[5ei3]], [[Resolution\|resolution]] 1.71Å' scene=''>
-	~~Authors~~: ~~Nowicki~~, M.W., ~~Walkinshaw~~, M.D., ~~Fischer~~, P.M.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[5ei3]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EI3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5EI3 FirstGlance]. <br>
-	~~Description~~: Co-~~crystal structure~~ of ~~eIF4E with nucleotide mimetic inhibitor~~.	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5O8:~{N}-[[(2~{R},3~{S},4~{R},5~{R})-5-[2-AZANYL-6-OXIDANYLIDENE-7-(PHENYLMETHYL)-1~{H}-PURIN-7-IUM-9-YL]-3,4-BIS(OXIDANYL)OXOLAN-2-YL]METHYL]-1,1,1-TRIS(FLUORANYL)METHANESULFONAMIDE'>5O8</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=5ei3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ei3 OCA], [http://pdbe.org/5ei3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ei3 RCSB], [http://www.ebi.ac.uk/pdbsum/5ei3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ei3 ProSAT]</span></td></tr>
-	[[Category: Nowicki, M.W]]	+	</table>
-	[[Category: ~~Fischer~~, P.M]]	+	== Function ==
-	[[Category: ~~Walkinshaw, M.D~~]]	+	[[http://www.uniprot.org/uniprot/IF4E_HUMAN IF4E_HUMAN]] Its translation stimulation activity is repressed by binding to the complex CYFIP1-FMR1 (By similarity). Recognizes and binds the 7-methylguanosine-containing mRNA cap during an early step in the initiation of protein synthesis and facilitates ribosome binding by inducing the unwinding of the mRNAs secondary structures. Component of the CYFIP1-EIF4E-FMR1 complex which binds to the mRNA cap and mediates translational repression. In the CYFIP1-EIF4E-FMR1 complex this subunit mediates the binding to the mRNA cap.<ref>PMID:16271312</ref>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Fischer, P M]]
		+	[[Category: Nowicki, M W]]
		+	[[Category: Walkinshaw, M D]]
		+	[[Category: Complex]]
		+	[[Category: Eif4e]]
		+	[[Category: Inhibitor]]
		+	[[Category: Translation]]

OCA: Protected "5ei3" [edit=sysop:move=sysop]

OCA — Tue, 01 Dec 2015 02:52:13 GMT

Protected "5ei3" [edit=sysop:move=sysop]

←Older revision

Revision as of 02:52, 1 December 2015

OCA: New page: '''Unreleased structure''' The entry 5ei3 is ON HOLD until Paper Publication Authors: Nowicki, M.W., Walkinshaw, M.D., Fischer, P.M. Description: Co-crystal structure of eIF4E with nuc...

OCA — Tue, 01 Dec 2015 02:52:12 GMT

New page: '''Unreleased structure''' The entry 5ei3 is ON HOLD until Paper Publication Authors: Nowicki, M.W., Walkinshaw, M.D., Fischer, P.M. Description: Co-crystal structure of eIF4E with nuc...

New page

'''Unreleased structure'''

The entry 5ei3 is ON HOLD until Paper Publication

Authors: Nowicki, M.W., Walkinshaw, M.D., Fischer, P.M.

Description: Co-crystal structure of eIF4E with nucleotide mimetic inhibitor.
[[Category: Unreleased Structures]]
[[Category: Nowicki, M.W]]
[[Category: Fischer, P.M]]
[[Category: Walkinshaw, M.D]]