6cjy - Revision history

OCA at 08:57, 11 November 2020

OCA — Wed, 11 Nov 2020 08:57:57 GMT

←Older revision		Revision as of 08:57, 11 November 2020
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	==Crystal Structure of Mnk2-D228G in complex with Inhibitor==		==Crystal Structure of Mnk2-D228G in complex with Inhibitor==
-	<StructureSection load='6cjy' size='340' side='right' caption='[[6cjy]], [[Resolution\|resolution]] 3.05Å' scene=''>	+	<StructureSection load='6cjy' size='340' side='right'caption='[[6cjy]], [[Resolution\|resolution]] 3.05Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6cjy]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CJY OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6CJY FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6cjy]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CJY OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6CJY FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=F4J:5-[(7H-purin-6-yl)amino]-1H-isoindol-1-one'>F4J</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=F4J:5-[(7H-purin-6-yl)amino]-1H-isoindol-1-one'>F4J</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6cj5\|6cj5]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6cj5\|6cj5]]</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </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=6cjy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cjy OCA], [http://pdbe.org/6cjy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6cjy RCSB], [http://www.ebi.ac.uk/pdbsum/6cjy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6cjy ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6cjy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cjy OCA], [http://pdbe.org/6cjy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6cjy RCSB], [http://www.ebi.ac.uk/pdbsum/6cjy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6cjy ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 20:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 6cjy" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6cjy" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Serine/threonine protein kinase 3D structures\|Serine/threonine protein kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Han, Q]]		[[Category: Han, Q]]
	[[Category: Mnk2 inhibitor]]		[[Category: Mnk2 inhibitor]]
	[[Category: Transferase-transferase inhibitor complex]]		[[Category: Transferase-transferase inhibitor complex]]

OCA at 06:18, 9 May 2018

OCA — Wed, 09 May 2018 06:18:50 GMT

←Older revision		Revision as of 06:18, 9 May 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6cjy is ~~ON HOLD~~	+	==Crystal Structure of Mnk2-D228G in complex with Inhibitor==
		+	<StructureSection load='6cjy' size='340' side='right' caption='[[6cjy]], [[Resolution\|resolution]] 3.05Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6cjy]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CJY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CJY FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=F4J:5-[(7H-purin-6-yl)amino]-1H-isoindol-1-one'>F4J</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6cj5\|6cj5]]</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </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=6cjy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cjy OCA], [http://pdbe.org/6cjy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6cjy RCSB], [http://www.ebi.ac.uk/pdbsum/6cjy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6cjy ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/MKNK2_HUMAN MKNK2_HUMAN]] Serine/threonine-protein kinase that phosphorylates SFPQ/PSF, HNRNPA1 and EIF4E. May play a role in the response to environmental stress and cytokines. Appears to regulate translation by phosphorylating EIF4E, thus increasing the affinity of this protein for the 7-methylguanosine-containing mRNA cap. Required for mediating PP2A-inhibition-induced EIF4E phosphorylation. Triggers EIF4E shuttling from cytoplasm to nucleus. Isoform 1 displays a high basal kinase activity, but isoform 2 exhibits a very low kinase activity. Acts as a mediator of the suppressive effects of IFNgamma on hematopoiesis. Negative regulator for signals that control generation of arsenic trioxide As(2)O(3)-dependent apoptosis and anti-leukemic responses. Involved in anti-apoptotic signaling in response to serum withdrawal.<ref>PMID:11154262</ref> <ref>PMID:11463832</ref> <ref>PMID:12897141</ref> <ref>PMID:16111636</ref> <ref>PMID:17965020</ref> <ref>PMID:18299328</ref> <ref>PMID:20823271</ref> <ref>PMID:20927323</ref> <ref>PMID:21149447</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Dysregulated translation of mRNA plays a major role in tumorigenesis. Mitogen-activated protein kinase interacting kinases (MNK)1/2 are key regulators of mRNA translation integrating signals from oncogenic and immune signaling pathways through phosphorylation of eIF4E and other mRNA binding proteins. Modulation of these key effector proteins regulates mRNA, which controls tumor/stromal cell signaling. Compound 23 (eFT508), an exquisitely selective, potent dual MNK1/2 inhibitor, was designed to assess the potential for control of oncogene signaling at the level of mRNA translation. The crystal structure-guided design leverages stereoelectronic interactions unique to MNK culminating in a novel pyridone-aminal structure described for the first time in the kinase literature. Compound 23 has potent in vivo antitumor activity in models of diffuse large cell B-cell lymphoma and solid tumors, suggesting that controlling dysregulated translation has real therapeutic potential. Compound 23 is currently being evaluated in Phase 2 clinical trials in solid tumors and lymphoma. Compound 23 is the first highly selective dual MNK inhibitor targeting dysregulated translation being assessed clinically.

-	~~Authors: Han~~, Q.	+	Structure-based Design of Pyridone-Aminal eFT508 Targeting Dysregulated Translation by Selective Mitogen-activated Protein Kinase Interacting Kinases 1 and 2 (MNK1/2) Inhibition.,Reich SH, Sprengeler PA, Chiang GG, Appleman JR, Chen J, Clarine J, Eam B, Ernst JT, Han Q, Goel VK, Han EZR, Huang V, Hung INJ, Jemison A, Jessen KA, Molter J, Murphy D, Neal M, Parker GS, Shaghafi M, Sperry S, Staunton J, Stumpf CR, Thompson PA, Tran C, Webber SE, Wegerski CJ, Zheng H, Webster KR J Med Chem. 2018 Apr 26;61(8):3516-3540. doi: 10.1021/acs.jmedchem.7b01795. Epub , 2018 Mar 29. PMID:29526098<ref>PMID:29526098</ref>

-	~~Description: Crystal Structure~~ of ~~Mnk2~~-~~D228G in complex with Inhibitor~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 6cjy" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Han, Q]]		[[Category: Han, Q]]
		+	[[Category: Mnk2 inhibitor]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA at 06:37, 2 May 2018

OCA — Wed, 02 May 2018 06:37:44 GMT

←Older revision		Revision as of 06:37, 2 May 2018
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	Authors: Han, Q.		Authors: Han, Q.

-	Description: Structure~~-based Design~~ of ~~Pyridone~~-~~aminal eFT2 Targeting Dysregulated Translation by Selective MNK1/2 Inhibition~~	+	Description: Crystal Structure of Mnk2-D228G in complex with Inhibitor
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Han, Q]]		[[Category: Han, Q]]

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

OCA — Thu, 08 Mar 2018 03:49:48 GMT

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

←Older revision

Revision as of 03:49, 8 March 2018

OCA: New page: '''Unreleased structure''' The entry 6cjy is ON HOLD Authors: Han, Q. Description: Structure-based Design of Pyridone-aminal eFT2 Targeting Dysregulated Translation by Selective MNK1/2...

OCA — Thu, 08 Mar 2018 03:49:47 GMT

New page: '''Unreleased structure''' The entry 6cjy is ON HOLD Authors: Han, Q. Description: Structure-based Design of Pyridone-aminal eFT2 Targeting Dysregulated Translation by Selective MNK1/2...

New page

'''Unreleased structure'''

The entry 6cjy is ON HOLD

Authors: Han, Q.

Description: Structure-based Design of Pyridone-aminal eFT2 Targeting Dysregulated Translation by Selective MNK1/2 Inhibition
[[Category: Unreleased Structures]]
[[Category: Han, Q]]