4d2w - Revision history

OCA at 11:17, 9 May 2024

2024-05-09T11:17:13Z

←Older revision		Revision as of 11:17, 9 May 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4d2w]] is a 4 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=4D2W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4D2W FirstGlance]. <br>		<table><tr><td colspan='2'>[[4d2w]] is a 4 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=4D2W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4D2W FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NF5:4-BROMO-N-(2,3,4,5-TETRAHYDRO-1H-3-BENZAZEPIN-7-YL)BENZAMIDE'>NF5</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]] 1.92Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NF5:4-BROMO-N-(2,3,4,5-TETRAHYDRO-1H-3-BENZAZEPIN-7-YL)BENZAMIDE'>NF5</scene></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=4d2w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4d2w OCA], [https://pdbe.org/4d2w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4d2w RCSB], [https://www.ebi.ac.uk/pdbsum/4d2w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4d2w 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=4d2w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4d2w OCA], [https://pdbe.org/4d2w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4d2w RCSB], [https://www.ebi.ac.uk/pdbsum/4d2w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4d2w ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[https://www.uniprot.org/uniprot/MELK_HUMAN MELK_HUMAN]] Note=Defects in MELK are associated with some cancers, such as brain or breast cancers. Expression is dramatically increased in aggressive undifferentiated tumors, correlating with poor patient outcome in breast and brain cancers, suggesting a role in tumor-initiating cells and proliferation via its function in cell proliferation regulation.	+	[https://www.uniprot.org/uniprot/MELK_HUMAN MELK_HUMAN] Note=Defects in MELK are associated with some cancers, such as brain or breast cancers. Expression is dramatically increased in aggressive undifferentiated tumors, correlating with poor patient outcome in breast and brain cancers, suggesting a role in tumor-initiating cells and proliferation via its function in cell proliferation regulation.
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/MELK_HUMAN MELK_HUMAN]] Serine/threonine-protein kinase involved in various processes such as cell cycle regulation, self-renewal of stem cells, apoptosis and splicing regulation. Has a broad substrate specificity; phosphorylates BCL2L14, CDC25B, MAP3K5/ASK1 and ZNF622. Acts as an activator of apoptosis by phosphorylating and activating MAP3K5/ASK1. Acts as a regulator of cell cycle, notably by mediating phosphorylation of CDC25B, promoting localization of CDC25B to the centrosome and the spindle poles during mitosis. Plays a key role in cell proliferation and carcinogenesis. Required for proliferation of embryonic and postnatal multipotent neural progenitors. Phosphorylates and inhibits BCL2L14, possibly leading to affect mammary carcinogenesis by mediating inhibition of the pro-apoptotic function of BCL2L14. Also involved in the inhibition of spliceosome assembly during mitosis by phosphorylating ZNF622, thereby contributing to its redirection to the nucleus. May also play a role in primitive hematopoiesis.<ref>PMID:11802789</ref> <ref>PMID:12400006</ref> <ref>PMID:14699119</ref> <ref>PMID:15908796</ref> <ref>PMID:16216881</ref> <ref>PMID:17280616</ref>	+	[https://www.uniprot.org/uniprot/MELK_HUMAN MELK_HUMAN] Serine/threonine-protein kinase involved in various processes such as cell cycle regulation, self-renewal of stem cells, apoptosis and splicing regulation. Has a broad substrate specificity; phosphorylates BCL2L14, CDC25B, MAP3K5/ASK1 and ZNF622. Acts as an activator of apoptosis by phosphorylating and activating MAP3K5/ASK1. Acts as a regulator of cell cycle, notably by mediating phosphorylation of CDC25B, promoting localization of CDC25B to the centrosome and the spindle poles during mitosis. Plays a key role in cell proliferation and carcinogenesis. Required for proliferation of embryonic and postnatal multipotent neural progenitors. Phosphorylates and inhibits BCL2L14, possibly leading to affect mammary carcinogenesis by mediating inhibition of the pro-apoptotic function of BCL2L14. Also involved in the inhibition of spliceosome assembly during mitosis by phosphorylating ZNF622, thereby contributing to its redirection to the nucleus. May also play a role in primitive hematopoiesis.<ref>PMID:11802789</ref> <ref>PMID:12400006</ref> <ref>PMID:14699119</ref> <ref>PMID:15908796</ref> <ref>PMID:16216881</ref> <ref>PMID:17280616</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 07:44, 14 September 2022

2022-09-14T07:44:57Z

←Older revision		Revision as of 07:44, 14 September 2022
Line 3:		Line 3:
	<StructureSection load='4d2w' size='340' side='right'caption='[[4d2w]], [[Resolution\|resolution]] 1.92Å' scene=''>		<StructureSection load='4d2w' size='340' side='right'caption='[[4d2w]], [[Resolution\|resolution]] 1.92Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4d2w]] is a 4 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=4D2W OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4D2W FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4d2w]] is a 4 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=4D2W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4D2W FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NF5:4-BROMO-N-(2,3,4,5-TETRAHYDRO-1H-3-BENZAZEPIN-7-YL)BENZAMIDE'>NF5</scene>~~</td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NF5:4-BROMO-N-(2,3,4,5-TETRAHYDRO-1H-3-BENZAZEPIN-7-YL)BENZAMIDE'>NF5</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4d2p\|4d2p]], [[4d2t\|4d2t]], [[4d2v\|4d2v]], [[4ump\|4ump]], [[4umq\|4umq]], [[4umr\|4umr]]~~</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=4d2w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4d2w OCA], [https://pdbe.org/4d2w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4d2w RCSB], [https://www.ebi.ac.uk/pdbsum/4d2w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4d2w 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=4d2w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4d2w OCA], [~~http~~://pdbe.org/4d2w PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4d2w RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4d2w PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4d2w ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[[~~http~~://www.uniprot.org/uniprot/MELK_HUMAN MELK_HUMAN]] Note=Defects in MELK are associated with some cancers, such as brain or breast cancers. Expression is dramatically increased in aggressive undifferentiated tumors, correlating with poor patient outcome in breast and brain cancers, suggesting a role in tumor-initiating cells and proliferation via its function in cell proliferation regulation.	+	[[https://www.uniprot.org/uniprot/MELK_HUMAN MELK_HUMAN]] Note=Defects in MELK are associated with some cancers, such as brain or breast cancers. Expression is dramatically increased in aggressive undifferentiated tumors, correlating with poor patient outcome in breast and brain cancers, suggesting a role in tumor-initiating cells and proliferation via its function in cell proliferation regulation.
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/MELK_HUMAN MELK_HUMAN]] Serine/threonine-protein kinase involved in various processes such as cell cycle regulation, self-renewal of stem cells, apoptosis and splicing regulation. Has a broad substrate specificity; phosphorylates BCL2L14, CDC25B, MAP3K5/ASK1 and ZNF622. Acts as an activator of apoptosis by phosphorylating and activating MAP3K5/ASK1. Acts as a regulator of cell cycle, notably by mediating phosphorylation of CDC25B, promoting localization of CDC25B to the centrosome and the spindle poles during mitosis. Plays a key role in cell proliferation and carcinogenesis. Required for proliferation of embryonic and postnatal multipotent neural progenitors. Phosphorylates and inhibits BCL2L14, possibly leading to affect mammary carcinogenesis by mediating inhibition of the pro-apoptotic function of BCL2L14. Also involved in the inhibition of spliceosome assembly during mitosis by phosphorylating ZNF622, thereby contributing to its redirection to the nucleus. May also play a role in primitive hematopoiesis.<ref>PMID:11802789</ref> <ref>PMID:12400006</ref> <ref>PMID:14699119</ref> <ref>PMID:15908796</ref> <ref>PMID:16216881</ref> <ref>PMID:17280616</ref>	+	[[https://www.uniprot.org/uniprot/MELK_HUMAN MELK_HUMAN]] Serine/threonine-protein kinase involved in various processes such as cell cycle regulation, self-renewal of stem cells, apoptosis and splicing regulation. Has a broad substrate specificity; phosphorylates BCL2L14, CDC25B, MAP3K5/ASK1 and ZNF622. Acts as an activator of apoptosis by phosphorylating and activating MAP3K5/ASK1. Acts as a regulator of cell cycle, notably by mediating phosphorylation of CDC25B, promoting localization of CDC25B to the centrosome and the spindle poles during mitosis. Plays a key role in cell proliferation and carcinogenesis. Required for proliferation of embryonic and postnatal multipotent neural progenitors. Phosphorylates and inhibits BCL2L14, possibly leading to affect mammary carcinogenesis by mediating inhibition of the pro-apoptotic function of BCL2L14. Also involved in the inhibition of spliceosome assembly during mitosis by phosphorylating ZNF622, thereby contributing to its redirection to the nucleus. May also play a role in primitive hematopoiesis.<ref>PMID:11802789</ref> <ref>PMID:12400006</ref> <ref>PMID:14699119</ref> <ref>PMID:15908796</ref> <ref>PMID:16216881</ref> <ref>PMID:17280616</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 25:		Line 24:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Beke, L]]	+	[[Category: Beke L]]
-	[[Category: Berdini, V]]	+	[[Category: Berdini V]]
-	[[Category: Bonnet, P]]	+	[[Category: Bonnet P]]
-	[[Category: Brehmer, D]]	+	[[Category: Brehmer D]]
-	[[Category: Coyle~~, J E~~]]	+	[[Category: Coyle JE]]
-	[[Category: Day~~, P J~~]]	+	[[Category: Day PJ]]
-	[[Category: Frederickson, M]]	+	[[Category: Frederickson M]]
-	[[Category: Freyne~~, E J.E~~]]	+	[[Category: Freyne EJE]]
-	[[Category: Gilissen~~, R A.H J~~]]	+	[[Category: Gilissen RAHJ]]
-	[[Category: Hamlett~~, C C.F~~]]	+	[[Category: Hamlett CCF]]
-	[[Category: Howard, S]]	+	[[Category: Howard S]]
-	[[Category: Johnson~~, C N~~]]	+	[[Category: Johnson CN]]
-	[[Category: Linders~~, J T.M~~]]	+	[[Category: Linders JTM]]
-	[[Category: McMenamin, R]]	+	[[Category: McMenamin R]]
-	[[Category: Meerpoel, L]]	+	[[Category: Meerpoel L]]
-	[[Category: Patel, S]]	+	[[Category: Patel S]]
-	[[Category: Rees~~, D C~~]]	+	[[Category: Rees DC]]
-	[[Category: Sharff, A]]	+	[[Category: Sharff A]]
-	[[Category: Sommen, F]]	+	[[Category: Sommen F]]
-	[[Category: Wu, T]]	+	[[Category: Wu T]]
-	~~[[Category: Fragment based drug design]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 09:45, 5 February 2020

2020-02-05T09:45:38Z

←Older revision		Revision as of 09:45, 5 February 2020
Line 1:		Line 1:

	==Structure of MELK in complex with inhibitors==		==Structure of MELK in complex with inhibitors==
-	<StructureSection load='4d2w' size='340' side='right' caption='[[4d2w]], [[Resolution\|resolution]] 1.92Å' scene=''>	+	<StructureSection load='4d2w' size='340' side='right'caption='[[4d2w]], [[Resolution\|resolution]] 1.92Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4d2w]] is a 4 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=4D2W OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4D2W FirstGlance]. <br>		<table><tr><td colspan='2'>[[4d2w]] is a 4 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=4D2W OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4D2W FirstGlance]. <br>
Line 26:		Line 26:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Beke, L]]		[[Category: Beke, L]]
	[[Category: Berdini, V]]		[[Category: Berdini, V]]

OCA at 06:39, 4 April 2018

2018-04-04T06:39:00Z

←Older revision		Revision as of 06:39, 4 April 2018
Line 3:		Line 3:
	<StructureSection load='4d2w' size='340' side='right' caption='[[4d2w]], [[Resolution\|resolution]] 1.92Å' scene=''>		<StructureSection load='4d2w' size='340' side='right' caption='[[4d2w]], [[Resolution\|resolution]] 1.92Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4d2w]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4D2W OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4D2W FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4d2w]] is a 4 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=4D2W OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4D2W FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NF5:4-BROMO-N-(2,3,4,5-TETRAHYDRO-1H-3-BENZAZEPIN-7-YL)BENZAMIDE'>NF5</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NF5:4-BROMO-N-(2,3,4,5-TETRAHYDRO-1H-3-BENZAZEPIN-7-YL)BENZAMIDE'>NF5</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4d2p\|4d2p]], [[4d2t\|4d2t]], [[4d2v\|4d2v]], [[4ump\|4ump]], [[4umq\|4umq]], [[4umr\|4umr]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4d2p\|4d2p]], [[4d2t\|4d2t]], [[4d2v\|4d2v]], [[4ump\|4ump]], [[4umq\|4umq]], [[4umr\|4umr]]</td></tr>
Line 25:		Line 25:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Beke, L]]		[[Category: Beke, L]]
	[[Category: Berdini, V]]		[[Category: Berdini, V]]

OCA at 16:54, 2 January 2017

2017-01-02T16:54:17Z

←Older revision		Revision as of 16:54, 2 January 2017
Line 1:		Line 1:
		+
	==Structure of MELK in complex with inhibitors==		==Structure of MELK in complex with inhibitors==
	<StructureSection load='4d2w' size='340' side='right' caption='[[4d2w]], [[Resolution\|resolution]] 1.92Å' scene=''>		<StructureSection load='4d2w' size='340' side='right' caption='[[4d2w]], [[Resolution\|resolution]] 1.92Å' scene=''>
Line 5:		Line 6:
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NF5:4-BROMO-N-(2,3,4,5-TETRAHYDRO-1H-3-BENZAZEPIN-7-YL)BENZAMIDE'>NF5</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NF5:4-BROMO-N-(2,3,4,5-TETRAHYDRO-1H-3-BENZAZEPIN-7-YL)BENZAMIDE'>NF5</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4d2p\|4d2p]], [[4d2t\|4d2t]], [[4d2v\|4d2v]], [[4ump\|4ump]], [[4umq\|4umq]], [[4umr\|4umr]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4d2p\|4d2p]], [[4d2t\|4d2t]], [[4d2v\|4d2v]], [[4ump\|4ump]], [[4umq\|4umq]], [[4umr\|4umr]]</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=4d2w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4d2w OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4d2w RCSB], [http://www.ebi.ac.uk/pdbsum/4d2w PDBsum]</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=4d2w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4d2w OCA], [http://pdbe.org/4d2w PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4d2w RCSB], [http://www.ebi.ac.uk/pdbsum/4d2w PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4d2w ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 19:		Line 20:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 4d2w" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 10:55, 28 January 2015

2015-01-28T10:55:40Z

←Older revision		Revision as of 10:55, 28 January 2015
Line 11:		Line 11:
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/MELK_HUMAN MELK_HUMAN]] Serine/threonine-protein kinase involved in various processes such as cell cycle regulation, self-renewal of stem cells, apoptosis and splicing regulation. Has a broad substrate specificity; phosphorylates BCL2L14, CDC25B, MAP3K5/ASK1 and ZNF622. Acts as an activator of apoptosis by phosphorylating and activating MAP3K5/ASK1. Acts as a regulator of cell cycle, notably by mediating phosphorylation of CDC25B, promoting localization of CDC25B to the centrosome and the spindle poles during mitosis. Plays a key role in cell proliferation and carcinogenesis. Required for proliferation of embryonic and postnatal multipotent neural progenitors. Phosphorylates and inhibits BCL2L14, possibly leading to affect mammary carcinogenesis by mediating inhibition of the pro-apoptotic function of BCL2L14. Also involved in the inhibition of spliceosome assembly during mitosis by phosphorylating ZNF622, thereby contributing to its redirection to the nucleus. May also play a role in primitive hematopoiesis.<ref>PMID:11802789</ref> <ref>PMID:12400006</ref> <ref>PMID:14699119</ref> <ref>PMID:15908796</ref> <ref>PMID:16216881</ref> <ref>PMID:17280616</ref>		[[http://www.uniprot.org/uniprot/MELK_HUMAN MELK_HUMAN]] Serine/threonine-protein kinase involved in various processes such as cell cycle regulation, self-renewal of stem cells, apoptosis and splicing regulation. Has a broad substrate specificity; phosphorylates BCL2L14, CDC25B, MAP3K5/ASK1 and ZNF622. Acts as an activator of apoptosis by phosphorylating and activating MAP3K5/ASK1. Acts as a regulator of cell cycle, notably by mediating phosphorylation of CDC25B, promoting localization of CDC25B to the centrosome and the spindle poles during mitosis. Plays a key role in cell proliferation and carcinogenesis. Required for proliferation of embryonic and postnatal multipotent neural progenitors. Phosphorylates and inhibits BCL2L14, possibly leading to affect mammary carcinogenesis by mediating inhibition of the pro-apoptotic function of BCL2L14. Also involved in the inhibition of spliceosome assembly during mitosis by phosphorylating ZNF622, thereby contributing to its redirection to the nucleus. May also play a role in primitive hematopoiesis.<ref>PMID:11802789</ref> <ref>PMID:12400006</ref> <ref>PMID:14699119</ref> <ref>PMID:15908796</ref> <ref>PMID:16216881</ref> <ref>PMID:17280616</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Fragment-based drug design was successfully applied to maternal embryonic leucine zipper kinase (MELK). A low affinity (160 muM) fragment hit was identified, which bound to the hinge region with an atypical binding mode, and this was optimized using structure-based design into a low-nanomolar and cell-penetrant inhibitor, with a good selectivity profile, suitable for use as a chemical probe for elucidation of MELK biology.
		+
		+	Fragment-based discovery of type I inhibitors of maternal embryonic leucine zipper kinase.,Johnson CN, Berdini V, Beke L, Bonnet P, Brehmer D, Coyle JE, Day PJ, Frederickson M, Freyne EJ, Gilissen RA, Hamlett CC, Howard S, Meerpoel L, McMenamin R, Patel S, Rees DC, Sharff A, Sommen F, Wu T, Linders JT ACS Med Chem Lett. 2014 May 23;6(1):25-30. doi: 10.1021/ml5001245. eCollection, 2015 Jan 8. PMID:25589925<ref>PMID:25589925</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 10:35, 20 January 2015

2015-01-20T10:35:46Z

←Older revision		Revision as of 10:35, 20 January 2015
Line 15:		Line 15:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Beke, L.]]	+	[[Category: Beke, L]]
-	[[Category: Berdini, V.]]	+	[[Category: Berdini, V]]
-	[[Category: Bonnet, P.]]	+	[[Category: Bonnet, P]]
-	[[Category: Brehmer, D.]]	+	[[Category: Brehmer, D]]
-	[[Category: Coyle, J E.]]	+	[[Category: Coyle, J E]]
-	[[Category: Day, P J.]]	+	[[Category: Day, P J]]
-	[[Category: Frederickson, M.]]	+	[[Category: Frederickson, M]]
-	[[Category: Freyne, E J.E.]]	+	[[Category: Freyne, E J.E]]
-	[[Category: Gilissen, R A.H J.]]	+	[[Category: Gilissen, R A.H J]]
-	[[Category: Hamlett, C C.F.]]	+	[[Category: Hamlett, C C.F]]
-	[[Category: Howard, S.]]	+	[[Category: Howard, S]]
-	[[Category: Johnson, C N.]]	+	[[Category: Johnson, C N]]
-	[[Category: Linders, J T.M.]]	+	[[Category: Linders, J T.M]]
-	[[Category: McMenamin, R.]]	+	[[Category: McMenamin, R]]
-	[[Category: Meerpoel, L.]]	+	[[Category: Meerpoel, L]]
-	[[Category: Patel, S.]]	+	[[Category: Patel, S]]
-	[[Category: Rees, D C.]]	+	[[Category: Rees, D C]]
-	[[Category: Sharff, A.]]	+	[[Category: Sharff, A]]
-	[[Category: Sommen, F.]]	+	[[Category: Sommen, F]]
-	[[Category: Wu, T.]]	+	[[Category: Wu, T]]
	[[Category: Fragment based drug design]]		[[Category: Fragment based drug design]]
	[[Category: Transferase]]		[[Category: Transferase]]

OCA at 07:47, 8 October 2014

2014-10-08T07:47:54Z

←Older revision		Revision as of 07:47, 8 October 2014
Line 1:		Line 1:
-	'''~~Unreleased~~ structure'''	+	==Structure of MELK in complex with inhibitors==
-		+	<StructureSection load='4d2w' size='340' side='right' caption='[[4d2w]], [[Resolution\|resolution]] 1.92Å' scene=''>
-	~~The entry~~ 4d2w is ~~ON HOLD until Paper Publication~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[4d2w]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4D2W OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4D2W FirstGlance]. <br>
-	~~Authors~~: ~~Johnson~~, C.N., ~~Berdini~~, V., Beke, L., Bonnet, P., Brehmer, D., Coyle, J.E., Day, P.J., Frederickson, M., Freyne, E.J.E., Gilissen, R.A.H.J., Hamlett, C.C.F., Howard, S., ~~Meerpoel, L~~., McMenamin, R., Patel, S., Rees, D.C., Sharff, A., Sommen, F., Wu, T.~~, Linders, J.T.M., ,~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NF5:4-BROMO-N-(2,3,4,5-TETRAHYDRO-1H-3-BENZAZEPIN-7-YL)BENZAMIDE'>NF5</scene></td></tr>
-		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4d2p\|4d2p]], [[4d2t\|4d2t]], [[4d2v\|4d2v]], [[4ump\|4ump]], [[4umq\|4umq]], [[4umr\|4umr]]</td></tr>
-	~~Description~~: ~~Structure of MELK in complex with inhibitors~~	+	<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=4d2w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4d2w OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4d2w RCSB], [http://www.ebi.ac.uk/pdbsum/4d2w PDBsum]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/MELK_HUMAN MELK_HUMAN]] Note=Defects in MELK are associated with some cancers, such as brain or breast cancers. Expression is dramatically increased in aggressive undifferentiated tumors, correlating with poor patient outcome in breast and brain cancers, suggesting a role in tumor-initiating cells and proliferation via its function in cell proliferation regulation.
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/MELK_HUMAN MELK_HUMAN]] Serine/threonine-protein kinase involved in various processes such as cell cycle regulation, self-renewal of stem cells, apoptosis and splicing regulation. Has a broad substrate specificity; phosphorylates BCL2L14, CDC25B, MAP3K5/ASK1 and ZNF622. Acts as an activator of apoptosis by phosphorylating and activating MAP3K5/ASK1. Acts as a regulator of cell cycle, notably by mediating phosphorylation of CDC25B, promoting localization of CDC25B to the centrosome and the spindle poles during mitosis. Plays a key role in cell proliferation and carcinogenesis. Required for proliferation of embryonic and postnatal multipotent neural progenitors. Phosphorylates and inhibits BCL2L14, possibly leading to affect mammary carcinogenesis by mediating inhibition of the pro-apoptotic function of BCL2L14. Also involved in the inhibition of spliceosome assembly during mitosis by phosphorylating ZNF622, thereby contributing to its redirection to the nucleus. May also play a role in primitive hematopoiesis.<ref>PMID:11802789</ref> <ref>PMID:12400006</ref> <ref>PMID:14699119</ref> <ref>PMID:15908796</ref> <ref>PMID:16216881</ref> <ref>PMID:17280616</ref>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Beke, L.]]
		+	[[Category: Berdini, V.]]
		+	[[Category: Bonnet, P.]]
		+	[[Category: Brehmer, D.]]
		+	[[Category: Coyle, J E.]]
		+	[[Category: Day, P J.]]
		+	[[Category: Frederickson, M.]]
		+	[[Category: Freyne, E J.E.]]
		+	[[Category: Gilissen, R A.H J.]]
		+	[[Category: Hamlett, C C.F.]]
		+	[[Category: Howard, S.]]
		+	[[Category: Johnson, C N.]]
		+	[[Category: Linders, J T.M.]]
		+	[[Category: McMenamin, R.]]
		+	[[Category: Meerpoel, L.]]
		+	[[Category: Patel, S.]]
		+	[[Category: Rees, D C.]]
		+	[[Category: Sharff, A.]]
		+	[[Category: Sommen, F.]]
		+	[[Category: Wu, T.]]
		+	[[Category: Fragment based drug design]]
		+	[[Category: Transferase]]

OCA at 22:47, 1 October 2014

2014-10-01T22:47:05Z

←Older revision		Revision as of 22:47, 1 October 2014
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4d2w is ON HOLD	+	The entry 4d2w is ON HOLD until Paper Publication

	Authors: Johnson, C.N., Berdini, V., Beke, L., Bonnet, P., Brehmer, D., Coyle, J.E., Day, P.J., Frederickson, M., Freyne, E.J.E., Gilissen, R.A.H.J., Hamlett, C.C.F., Howard, S., Meerpoel, L., McMenamin, R., Patel, S., Rees, D.C., Sharff, A., Sommen, F., Wu, T., Linders, J.T.M., ,		Authors: Johnson, C.N., Berdini, V., Beke, L., Bonnet, P., Brehmer, D., Coyle, J.E., Day, P.J., Frederickson, M., Freyne, E.J.E., Gilissen, R.A.H.J., Hamlett, C.C.F., Howard, S., Meerpoel, L., McMenamin, R., Patel, S., Rees, D.C., Sharff, A., Sommen, F., Wu, T., Linders, J.T.M., ,

	Description: Structure of MELK in complex with inhibitors		Description: Structure of MELK in complex with inhibitors

OCA: Protected "4d2w" [edit=sysop:move=sysop]

2014-05-21T07:33:54Z

Protected "4d2w" [edit=sysop:move=sysop]

←Older revision

Revision as of 07:33, 21 May 2014