6aqb - Revision history

OCA at 14:17, 13 March 2024

OCA — Wed, 13 Mar 2024 14:17:58 GMT

←Older revision		Revision as of 14:17, 13 March 2024
Line 1:		Line 1:

	==Structure of the SH3 domain of MLK3 bound to peptide generated from phage display==		==Structure of the SH3 domain of MLK3 bound to peptide generated from phage display==
-	<StructureSection load='6aqb' size='340' side='right' caption='[[6aqb]], [[Resolution\|resolution]] 1.50Å' scene=''>	+	<StructureSection load='6aqb' size='340' side='right'caption='[[6aqb]], [[Resolution\|resolution]] 1.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6aqb]] 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=6AQB OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6AQB FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6aqb]] is a 2 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=6AQB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6AQB FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat">~~<scene name='pdbligand=EDO:1,2~~-~~ETHANEDIOL'>EDO</scene>~~, ~~<scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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]] 1.5Å</td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat"~~>MAP3K11, MLK3, PTK1, SPRK ([http://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=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></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_kinase Mitogen-activated protein kinase kinase kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.25 2.7.11.25] </~~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=6aqb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6aqb OCA], [https://pdbe.org/6aqb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6aqb RCSB], [https://www.ebi.ac.uk/pdbsum/6aqb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6aqb 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=6aqb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6aqb OCA], [~~http~~://pdbe.org/6aqb PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6aqb RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6aqb PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6aqb ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/M3K11_HUMAN M3K11_HUMAN]] Activates the JUN N-terminal pathway. Required for serum-stimulated cell proliferation and for mitogen and cytokine activation of MAPK14 (p38), MAPK3 (ERK) and MAPK8 (JNK1) through phosphorylation and activation of MAP2K4/MKK4 and MAP2K7/MKK7. Plays a role in mitogen-stimulated phosphorylation and activation of BRAF, but does not phosphorylate BRAF directly. Influences microtubule organization during the cell cycle.<ref>PMID:12529434</ref> <ref>PMID:15258589</ref> <ref>PMID:8195146</ref> <ref>PMID:9003778</ref>	+	[https://www.uniprot.org/uniprot/M3K11_HUMAN M3K11_HUMAN] Activates the JUN N-terminal pathway. Required for serum-stimulated cell proliferation and for mitogen and cytokine activation of MAPK14 (p38), MAPK3 (ERK) and MAPK8 (JNK1) through phosphorylation and activation of MAP2K4/MKK4 and MAP2K7/MKK7. Plays a role in mitogen-stimulated phosphorylation and activation of BRAF, but does not phosphorylate BRAF directly. Influences microtubule organization during the cell cycle.<ref>PMID:12529434</ref> <ref>PMID:15258589</ref> <ref>PMID:8195146</ref> <ref>PMID:9003778</ref>
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	Mixed-lineage kinase 3 (MLK3; also known as MAP3K11) is a Ser/Thr protein kinase widely expressed in normal and cancerous tissues, including brain, lung, liver, heart, and skeletal muscle tissues. Its Src homology 3 (SH3) domain has been implicated in MLK3 autoinhibition and interactions with other proteins, including those from viruses. The MLK3 SH3 domain contains a six-amino-acid insert corresponding to the n-Src insert, suggesting that MLK3 may bind additional peptides. Here, affinity selection of a phage-displayed combinatorial peptide library for MLK3's SH3 domain yielded a 13-mer peptide, designated "MLK3 SH3-interacting peptide" (MIP). Unlike most SH3 domain peptide ligands, MIP contained a single proline. The 1.2-A crystal structure of the MIP-bound SH3 domain revealed that the peptide adopts a beta-hairpin shape, and comparison with a 1.5-A apo SH3 domain structure disclosed that the n-Src loop in SH3 undergoes an MIP-induced conformational change. A 1.5-A structure of the MLK3 SH3 domain bound to a canonical proline-rich peptide from hepatitis C virus nonstructural 5A (NS5A) protein revealed that it and MIP bind the SH3 domain at two distinct sites, but biophysical analyses suggested that the two peptides compete with each other for SH3 binding. Moreover, SH3 domains of MLK1 and MLK4, but not MLK2, also bound MIP, suggesting that the MLK1-4 family may be differentially regulated through their SH3 domains. In summary, we have identified two distinct peptide-binding sites in the SH3 domain of MLK3, providing critical insights into mechanisms of ligand binding by the MLK family of kinases.	+
-		+
-	Identification of two distinct peptide-binding pockets in the SH3 domain of human mixed-lineage kinase 3.,Kokoszka ME, Kall SL, Khosla S, McGinnis JE, Lavie A, Kay BK J Biol Chem. 2018 Aug 31;293(35):13553-13565. doi: 10.1074/jbc.RA117.000262. Epub, 2018 Jul 6. PMID:29980598<ref>PMID:29980598</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 6aqb" style="background-color:#fffaf0;"></div~~>	+
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Mitogen-activated protein kinase kinase kinase~~]]	+	[[Category: Large Structures]]
-	[[Category: Kall~~, S K~~]]	+	[[Category: Kall SK]]
-	[[Category: Lavie, A]]	+	[[Category: Lavie A]]
-	~~[[Category: Mlk3]]~~	+
-	~~[[Category: Phage display]]~~	+
-	~~[[Category: Sh3]]~~	+
-	~~[[Category: Signalling protein]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 08:35, 26 December 2018

OCA — Wed, 26 Dec 2018 08:35:27 GMT

←Older revision		Revision as of 08:35, 26 December 2018
Line 3:		Line 3:
	<StructureSection load='6aqb' size='340' side='right' caption='[[6aqb]], [[Resolution\|resolution]] 1.50Å' scene=''>		<StructureSection load='6aqb' size='340' side='right' caption='[[6aqb]], [[Resolution\|resolution]] 1.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6aqb]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AQB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6AQB FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6aqb]] 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=6AQB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6AQB FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MAP3K11, MLK3, PTK1, SPRK ([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/Mitogen-activated_protein_kinase_kinase_kinase Mitogen-activated protein kinase kinase kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.25 2.7.11.25] </span></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_kinase Mitogen-activated protein kinase kinase kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.25 2.7.11.25] </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=6aqb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6aqb OCA], [http://pdbe.org/6aqb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6aqb RCSB], [http://www.ebi.ac.uk/pdbsum/6aqb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6aqb 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=6aqb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6aqb OCA], [http://pdbe.org/6aqb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6aqb RCSB], [http://www.ebi.ac.uk/pdbsum/6aqb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6aqb ProSAT]</span></td></tr>
Line 10:		Line 11:
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/M3K11_HUMAN M3K11_HUMAN]] Activates the JUN N-terminal pathway. Required for serum-stimulated cell proliferation and for mitogen and cytokine activation of MAPK14 (p38), MAPK3 (ERK) and MAPK8 (JNK1) through phosphorylation and activation of MAP2K4/MKK4 and MAP2K7/MKK7. Plays a role in mitogen-stimulated phosphorylation and activation of BRAF, but does not phosphorylate BRAF directly. Influences microtubule organization during the cell cycle.<ref>PMID:12529434</ref> <ref>PMID:15258589</ref> <ref>PMID:8195146</ref> <ref>PMID:9003778</ref>		[[http://www.uniprot.org/uniprot/M3K11_HUMAN M3K11_HUMAN]] Activates the JUN N-terminal pathway. Required for serum-stimulated cell proliferation and for mitogen and cytokine activation of MAPK14 (p38), MAPK3 (ERK) and MAPK8 (JNK1) through phosphorylation and activation of MAP2K4/MKK4 and MAP2K7/MKK7. Plays a role in mitogen-stimulated phosphorylation and activation of BRAF, but does not phosphorylate BRAF directly. Influences microtubule organization during the cell cycle.<ref>PMID:12529434</ref> <ref>PMID:15258589</ref> <ref>PMID:8195146</ref> <ref>PMID:9003778</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Mixed-lineage kinase 3 (MLK3; also known as MAP3K11) is a Ser/Thr protein kinase widely expressed in normal and cancerous tissues, including brain, lung, liver, heart, and skeletal muscle tissues. Its Src homology 3 (SH3) domain has been implicated in MLK3 autoinhibition and interactions with other proteins, including those from viruses. The MLK3 SH3 domain contains a six-amino-acid insert corresponding to the n-Src insert, suggesting that MLK3 may bind additional peptides. Here, affinity selection of a phage-displayed combinatorial peptide library for MLK3's SH3 domain yielded a 13-mer peptide, designated "MLK3 SH3-interacting peptide" (MIP). Unlike most SH3 domain peptide ligands, MIP contained a single proline. The 1.2-A crystal structure of the MIP-bound SH3 domain revealed that the peptide adopts a beta-hairpin shape, and comparison with a 1.5-A apo SH3 domain structure disclosed that the n-Src loop in SH3 undergoes an MIP-induced conformational change. A 1.5-A structure of the MLK3 SH3 domain bound to a canonical proline-rich peptide from hepatitis C virus nonstructural 5A (NS5A) protein revealed that it and MIP bind the SH3 domain at two distinct sites, but biophysical analyses suggested that the two peptides compete with each other for SH3 binding. Moreover, SH3 domains of MLK1 and MLK4, but not MLK2, also bound MIP, suggesting that the MLK1-4 family may be differentially regulated through their SH3 domains. In summary, we have identified two distinct peptide-binding sites in the SH3 domain of MLK3, providing critical insights into mechanisms of ligand binding by the MLK family of kinases.
		+
		+	Identification of two distinct peptide-binding pockets in the SH3 domain of human mixed-lineage kinase 3.,Kokoszka ME, Kall SL, Khosla S, McGinnis JE, Lavie A, Kay BK J Biol Chem. 2018 Aug 31;293(35):13553-13565. doi: 10.1074/jbc.RA117.000262. Epub, 2018 Jul 6. PMID:29980598<ref>PMID:29980598</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6aqb" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Mitogen-activated protein kinase kinase kinase]]		[[Category: Mitogen-activated protein kinase kinase kinase]]
	[[Category: Kall, S K]]		[[Category: Kall, S K]]

OCA at 07:10, 4 July 2018

OCA — Wed, 04 Jul 2018 07:10:14 GMT

←Older revision		Revision as of 07:10, 4 July 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6aqb is ~~ON HOLD~~	+	==Structure of the SH3 domain of MLK3 bound to peptide generated from phage display==
-		+	<StructureSection load='6aqb' size='340' side='right' caption='[[6aqb]], [[Resolution\|resolution]] 1.50Å' scene=''>
-	~~Authors~~: ~~Kall~~, S.K., ~~Lavie~~, A.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6aqb]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AQB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6AQB FirstGlance]. <br>
-	~~Description~~: ~~Structure of~~ the ~~SH3 domain~~ of ~~MLK3 bound to peptide generated from phage display~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	<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_kinase Mitogen-activated protein kinase kinase kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.25 2.7.11.25] </span></td></tr>
-	[[Category: Kall, S.K]]	+	<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=6aqb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6aqb OCA], [http://pdbe.org/6aqb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6aqb RCSB], [http://www.ebi.ac.uk/pdbsum/6aqb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6aqb ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/M3K11_HUMAN M3K11_HUMAN]] Activates the JUN N-terminal pathway. Required for serum-stimulated cell proliferation and for mitogen and cytokine activation of MAPK14 (p38), MAPK3 (ERK) and MAPK8 (JNK1) through phosphorylation and activation of MAP2K4/MKK4 and MAP2K7/MKK7. Plays a role in mitogen-stimulated phosphorylation and activation of BRAF, but does not phosphorylate BRAF directly. Influences microtubule organization during the cell cycle.<ref>PMID:12529434</ref> <ref>PMID:15258589</ref> <ref>PMID:8195146</ref> <ref>PMID:9003778</ref>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Mitogen-activated protein kinase kinase kinase]]
		+	[[Category: Kall, S K]]
	[[Category: Lavie, A]]		[[Category: Lavie, A]]
		+	[[Category: Mlk3]]
		+	[[Category: Phage display]]
		+	[[Category: Sh3]]
		+	[[Category: Signalling protein]]
		+	[[Category: Transferase]]

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

OCA — Wed, 27 Sep 2017 16:40:35 GMT

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

←Older revision

Revision as of 16:40, 27 September 2017

OCA: New page: '''Unreleased structure''' The entry 6aqb is ON HOLD Authors: Kall, S.K., Lavie, A. Description: Structure of the SH3 domain of MLK3 bound to peptide generated from phage display [[Cat...

OCA — Wed, 27 Sep 2017 16:40:34 GMT

New page: '''Unreleased structure''' The entry 6aqb is ON HOLD Authors: Kall, S.K., Lavie, A. Description: Structure of the SH3 domain of MLK3 bound to peptide generated from phage display [[Cat...

New page

'''Unreleased structure'''

The entry 6aqb is ON HOLD

Authors: Kall, S.K., Lavie, A.

Description: Structure of the SH3 domain of MLK3 bound to peptide generated from phage display
[[Category: Unreleased Structures]]
[[Category: Kall, S.K]]
[[Category: Lavie, A]]