5y8u - Revision history

OCA at 08:24, 22 November 2023

OCA — Wed, 22 Nov 2023 08:24:42 GMT

←Older revision		Revision as of 08:24, 22 November 2023
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	<StructureSection load='5y8u' size='340' side='right'caption='[[5y8u]], [[Resolution\|resolution]] 2.92Å' scene=''>		<StructureSection load='5y8u' size='340' side='right'caption='[[5y8u]], [[Resolution\|resolution]] 2.92Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5y8u]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5Y8U OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5Y8U FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5y8u]] 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=5Y8U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5Y8U FirstGlance]. <br>
-	</td></tr><tr id='~~activity~~'><td class="sblockLbl"><b>~~Activity~~:</b></td><td class="sblockDat"~~><span class~~=~~'plainlinks'~~>~~[http://en.wikipedia.org/wiki/Mitogen~~-~~activated_protein_kinase_kinase Mitogen-activated protein kinase kinase]~~, ~~with EC number~~ [~~http://www.brenda-enzymes.info/php/result_flat.php4?ecno=~~2.~~7.12.2 2.7.12.2] </span>~~</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]] 2.92Å</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=5y8u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5y8u OCA], [~~http~~://pdbe.org/5y8u PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5y8u RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5y8u PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5y8u 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=5y8u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5y8u OCA], [https://pdbe.org/5y8u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5y8u RCSB], [https://www.ebi.ac.uk/pdbsum/5y8u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5y8u ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/MP2K7_HUMAN MP2K7_HUMAN]] Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. With MAP2K4/MKK4, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the phosphorylation site in the Thr-Pro-Tyr motif. MAP2K4/MKK4 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The monophosphorylation of JNKs on the Thr residue is sufficient to increase JNK activity indicating that MAP2K7/MKK7 is important to trigger JNK activity, while the additional phosphorylation of the Tyr residue by MAP2K4/MKK4 ensures optimal JNK activation. Has a specific role in JNK signal transduction pathway activated by proinflammatory cytokines. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis.<ref>PMID:9372971</ref> <ref>PMID:9312068</ref> <ref>PMID:9535930</ref> [:]	+	[https://www.uniprot.org/uniprot/MP2K7_HUMAN MP2K7_HUMAN] Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. With MAP2K4/MKK4, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the phosphorylation site in the Thr-Pro-Tyr motif. MAP2K4/MKK4 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The monophosphorylation of JNKs on the Thr residue is sufficient to increase JNK activity indicating that MAP2K7/MKK7 is important to trigger JNK activity, while the additional phosphorylation of the Tyr residue by MAP2K4/MKK4 ensures optimal JNK activation. Has a specific role in JNK signal transduction pathway activated by proinflammatory cytokines. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis.<ref>PMID:9372971</ref> <ref>PMID:9312068</ref> <ref>PMID:9535930</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 5y8u" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5y8u" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Mitogen-activated protein kinase kinase 3D structures\|Mitogen-activated protein kinase kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Mitogen-activated protein kinase kinase]]~~	+	[[Category: Kinoshita T]]
-	[[Category: Kinoshita, T]]	+
-	~~[[Category: Protein kinase]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 09:13, 21 October 2020

OCA — Wed, 21 Oct 2020 09:13:15 GMT

←Older revision		Revision as of 09:13, 21 October 2020
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	==Crystal structure of the C276S mutant of MAP2K7==		==Crystal structure of the C276S mutant of MAP2K7==
-	<StructureSection load='5y8u' size='340' side='right' caption='[[5y8u]], [[Resolution\|resolution]] 2.92Å' scene=''>	+	<StructureSection load='5y8u' size='340' side='right'caption='[[5y8u]], [[Resolution\|resolution]] 2.92Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5y8u]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5Y8U OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5Y8U FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5y8u]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5Y8U OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5Y8U FirstGlance]. <br>
	</td></tr><tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase_kinase Mitogen-activated protein kinase kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.12.2 2.7.12.2] </span></td></tr>		</td></tr><tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase_kinase Mitogen-activated protein kinase kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.12.2 2.7.12.2] </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=5y8u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5y8u OCA], [http://pdbe.org/5y8u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5y8u RCSB], [http://www.ebi.ac.uk/pdbsum/5y8u PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5y8u 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=5y8u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5y8u OCA], [http://pdbe.org/5y8u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5y8u RCSB], [http://www.ebi.ac.uk/pdbsum/5y8u PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5y8u ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Mitogen-activated protein kinase kinase]]		[[Category: Mitogen-activated protein kinase kinase]]
	[[Category: Kinoshita, T]]		[[Category: Kinoshita, T]]
	[[Category: Protein kinase]]		[[Category: Protein kinase]]
	[[Category: Transferase]]		[[Category: Transferase]]

OCA at 06:50, 11 October 2017

OCA — Wed, 11 Oct 2017 06:50:34 GMT

←Older revision		Revision as of 06:50, 11 October 2017
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-	'''Unreleased structure'''

-	~~The entry~~ 5y8u is ~~ON HOLD until Paper~~ Publication	+	==Crystal structure of the C276S mutant of MAP2K7==
		+	<StructureSection load='5y8u' size='340' side='right' caption='[[5y8u]], [[Resolution\|resolution]] 2.92Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5y8u]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5Y8U OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5Y8U FirstGlance]. <br>
		+	</td></tr><tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase_kinase Mitogen-activated protein kinase kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.12.2 2.7.12.2] </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=5y8u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5y8u OCA], [http://pdbe.org/5y8u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5y8u RCSB], [http://www.ebi.ac.uk/pdbsum/5y8u PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5y8u ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/MP2K7_HUMAN MP2K7_HUMAN]] Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. With MAP2K4/MKK4, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the phosphorylation site in the Thr-Pro-Tyr motif. MAP2K4/MKK4 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The monophosphorylation of JNKs on the Thr residue is sufficient to increase JNK activity indicating that MAP2K7/MKK7 is important to trigger JNK activity, while the additional phosphorylation of the Tyr residue by MAP2K4/MKK4 ensures optimal JNK activation. Has a specific role in JNK signal transduction pathway activated by proinflammatory cytokines. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis.<ref>PMID:9372971</ref> <ref>PMID:9312068</ref> <ref>PMID:9535930</ref> [:]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Mitogen-activated protein kinase kinase 7 (MAP2K7) regulates stress and inflammatory responses, and is an attractive drug discovery target for several diseases including arthritis and cardiac hypertrophy. Intracellular proteins such as MAP2K7 are prone to aggregation due to cysteine-driven oxidation in in vitro experiments. MAP2K7 instability due to the four free cysteine residues on the molecular surface abrogated the crystal growth and led to a low-resolution structure with large residual errors. To acquire a higher resolution structure for promoting rational drug discovery, we explored stable mutants of MAP2K7 by replacing the surface cysteine residues, Cys147, Cys218, Cys276 and Cys296. Single-site mutations, except for Cys147, maintained the specific activity and increased the protein yield, while all the multi-site mutations massively reduced the activity. The C218S mutation drastically augmented the protein production and crystallographic resolution. Furthermore, the C218S crystals grown under microgravity in a space environment yielded a 1.3 A resolution structure, providing novel insights for drug discovery: the precisely assigned water molecules in the active site, the double conformations in the flexible region and the C-terminal extension bound to the N-terminal region of the adjacent molecules. The latter insight is likely to promote the production of allosteric MAP2K7 inhibitors.

-	~~Authors:~~ Kinoshita, T.	+	High-resolution structure discloses the potential for allosteric regulation of mitogen-activated protein kinase kinase 7.,Kinoshita T, Hashimoto T, Sogabe Y, Fukada H, Matsumoto T, Sawa M Biochem Biophys Res Commun. 2017 Sep 7. pii: S0006-291X(17)31785-0. doi:, 10.1016/j.bbrc.2017.09.025. PMID:28890347<ref>PMID:28890347</ref>

-	~~Description: Crystal structure~~ of the ~~C276S mutant~~ of ~~MAP2K7~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 5y8u" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Mitogen-activated protein kinase kinase]]
	[[Category: Kinoshita, T]]		[[Category: Kinoshita, T]]
		+	[[Category: Protein kinase]]
		+	[[Category: Transferase]]

OCA: Protected "5y8u" [edit=sysop:move=sysop]

OCA — Wed, 27 Sep 2017 16:16:45 GMT

Protected "5y8u" [edit=sysop:move=sysop]

←Older revision

Revision as of 16:16, 27 September 2017

OCA: New page: '''Unreleased structure''' The entry 5y8u is ON HOLD until Paper Publication Authors: Kinoshita, T. Description: Crystal structure of the C276S mutant of MAP2K7 [[Category: Unreleased ...

OCA — Wed, 27 Sep 2017 16:16:44 GMT

New page: '''Unreleased structure''' The entry 5y8u is ON HOLD until Paper Publication Authors: Kinoshita, T. Description: Crystal structure of the C276S mutant of MAP2K7 [[Category: Unreleased ...

New page

'''Unreleased structure'''

The entry 5y8u is ON HOLD until Paper Publication

Authors: Kinoshita, T.

Description: Crystal structure of the C276S mutant of MAP2K7
[[Category: Unreleased Structures]]
[[Category: Kinoshita, T]]