4umu - Revision history

OCA at 11:21, 9 May 2024

OCA — Thu, 09 May 2024 11:21:57 GMT

←Older revision		Revision as of 11:21, 9 May 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4umu]] 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=4UMU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4UMU FirstGlance]. <br>		<table><tr><td colspan='2'>[[4umu]] 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=4UMU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4UMU FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0V0:(2-ETHOXY-4-{[3-(ISOQUINOLIN-7-YL)PROP-2-YN-1-YL]OXY}PHENYL)METHANAMINIUM'>0V0</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]] 2.02Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0V0:(2-ETHOXY-4-{[3-(ISOQUINOLIN-7-YL)PROP-2-YN-1-YL]OXY}PHENYL)METHANAMINIUM'>0V0</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=4umu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4umu OCA], [https://pdbe.org/4umu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4umu RCSB], [https://www.ebi.ac.uk/pdbsum/4umu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4umu 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=4umu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4umu OCA], [https://pdbe.org/4umu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4umu RCSB], [https://www.ebi.ac.uk/pdbsum/4umu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4umu ProSAT]</span></td></tr>
	</table>		</table>

OCA at 08:29, 22 March 2023

OCA — Wed, 22 Mar 2023 08:29:43 GMT

←Older revision		Revision as of 08:29, 22 March 2023
Line 3:		Line 3:
	<StructureSection load='4umu' size='340' side='right'caption='[[4umu]], [[Resolution\|resolution]] 2.02Å' scene=''>		<StructureSection load='4umu' size='340' side='right'caption='[[4umu]], [[Resolution\|resolution]] 2.02Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4umu]] is a 1 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=4UMU OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4UMU FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4umu]] 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=4UMU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4UMU FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0V0:(2-ETHOXY-4-{[3-(ISOQUINOLIN-7-YL)PROP-2-YN-1-YL]OXY}PHENYL)METHANAMINIUM'>0V0</scene>~~</td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0V0:(2-ETHOXY-4-{[3-(ISOQUINOLIN-7-YL)PROP-2-YN-1-YL]OXY}PHENYL)METHANAMINIUM'>0V0</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4ump\|4ump]], [[4umq\|4umq]], [[4umr\|4umr]], [[4umt\|4umt]]~~</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=4umu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4umu OCA], [https://pdbe.org/4umu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4umu RCSB], [https://www.ebi.ac.uk/pdbsum/4umu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4umu 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=4umu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4umu OCA], [~~http~~://pdbe.org/4umu PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4umu RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4umu PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4umu 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: Kinase]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 09:15, 21 May 2019

OCA — Tue, 21 May 2019 09:15:15 GMT

←Older revision		Revision as of 09:15, 21 May 2019
Line 1:		Line 1:

	==Structure of MELK in complex with inhibitors==		==Structure of MELK in complex with inhibitors==
-	<StructureSection load='4umu' size='340' side='right' caption='[[4umu]], [[Resolution\|resolution]] 2.02Å' scene=''>	+	<StructureSection load='4umu' size='340' side='right'caption='[[4umu]], [[Resolution\|resolution]] 2.02Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4umu]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4UMU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4UMU FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4umu]] is a 1 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=4UMU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4UMU FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0V0:(2-ETHOXY-4-{[3-(ISOQUINOLIN-7-YL)PROP-2-YN-1-YL]OXY}PHENYL)METHANAMINIUM'>0V0</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0V0:(2-ETHOXY-4-{[3-(ISOQUINOLIN-7-YL)PROP-2-YN-1-YL]OXY}PHENYL)METHANAMINIUM'>0V0</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4ump\|4ump]], [[4umq\|4umq]], [[4umr\|4umr]], [[4umt\|4umt]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4ump\|4ump]], [[4umq\|4umq]], [[4umr\|4umr]], [[4umt\|4umt]]</td></tr>
Line 25:		Line 25:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Beke, L]]		[[Category: Beke, L]]
	[[Category: Berdini, V]]		[[Category: Berdini, V]]

OCA at 01:16, 19 January 2017

OCA — Thu, 19 Jan 2017 01:16:12 GMT

←Older revision		Revision as of 01:16, 19 January 2017
Line 1:		Line 1:
		+
	==Structure of MELK in complex with inhibitors==		==Structure of MELK in complex with inhibitors==
	<StructureSection load='4umu' size='340' side='right' caption='[[4umu]], [[Resolution\|resolution]] 2.02Å' scene=''>		<StructureSection load='4umu' size='340' side='right' caption='[[4umu]], [[Resolution\|resolution]] 2.02Å' scene=''>
Line 5:		Line 6:
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0V0:(2-ETHOXY-4-{[3-(ISOQUINOLIN-7-YL)PROP-2-YN-1-YL]OXY}PHENYL)METHANAMINIUM'>0V0</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0V0:(2-ETHOXY-4-{[3-(ISOQUINOLIN-7-YL)PROP-2-YN-1-YL]OXY}PHENYL)METHANAMINIUM'>0V0</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4ump\|4ump]], [[4umq\|4umq]], [[4umr\|4umr]], [[4umt\|4umt]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4ump\|4ump]], [[4umq\|4umq]], [[4umr\|4umr]], [[4umt\|4umt]]</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=4umu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4umu OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4umu RCSB], [http://www.ebi.ac.uk/pdbsum/4umu 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=4umu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4umu OCA], [http://pdbe.org/4umu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4umu RCSB], [http://www.ebi.ac.uk/pdbsum/4umu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4umu 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 4umu" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 10:44, 28 January 2015

OCA — Wed, 28 Jan 2015 10:44:47 GMT

←Older revision		Revision as of 10:44, 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 ==
		+	A novel Type II kinase inhibitor chemotype has been identified for maternal embryonic leucine zipper kinase (MELK) using structure-based ligand design. The strategy involved structural characterization of an induced DFG-out pocket by protein-ligand X-ray crystallography and incorporation of a slender linkage capable of bypassing a large gate-keeper residue, thus enabling design of molecules accessing both hinge and induced pocket regions. Optimization of an initial hit led to the identification of a low-nanomolar, cell-penetrant Type II inhibitor suitable for use as a chemical probe for MELK.
		+
		+	Structure-Based Design of Type II Inhibitors Applied to Maternal Embryonic Leucine Zipper Kinase.,Johnson CN, Adelinet C, Berdini V, Beke L, Bonnet P, Brehmer D, Calo F, Coyle JE, Day PJ, Frederickson M, Freyne EJ, Gilissen RA, Hamlett CC, Howard S, Meerpoel L, Mevellec L, McMenamin R, Pasquier E, Patel S, Rees DC, Linders JT ACS Med Chem Lett. 2014 May 23;6(1):31-6. doi: 10.1021/ml5001273. eCollection, 2015 Jan 8. PMID:25589926<ref>PMID:25589926</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 08:10, 25 January 2015

OCA — Sun, 25 Jan 2015 08:10:09 GMT

←Older revision		Revision as of 08:10, 25 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: Kinase]]		[[Category: Kinase]]
	[[Category: Transferase]]		[[Category: Transferase]]

OCA at 12:29, 22 October 2014

OCA — Wed, 22 Oct 2014 12:29:14 GMT

←Older revision		Revision as of 12:29, 22 October 2014
Line 1:		Line 1:
-	'''~~Unreleased~~ structure'''	+	==Structure of MELK in complex with inhibitors==
-		+	<StructureSection load='4umu' size='340' side='right' caption='[[4umu]], [[Resolution\|resolution]] 2.02Å' scene=''>
-	~~The entry~~ 4umu is ~~ON HOLD until Paper Publication~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[4umu]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4UMU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4UMU 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=0V0:(2-ETHOXY-4-{[3-(ISOQUINOLIN-7-YL)PROP-2-YN-1-YL]OXY}PHENYL)METHANAMINIUM'>0V0</scene></td></tr>
-		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4ump\|4ump]], [[4umq\|4umq]], [[4umr\|4umr]], [[4umt\|4umt]]</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=4umu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4umu OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4umu RCSB], [http://www.ebi.ac.uk/pdbsum/4umu 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: Kinase]]
		+	[[Category: Transferase]]

OCA at 06:45, 8 October 2014

OCA — Wed, 08 Oct 2014 06:45:08 GMT

←Older revision		Revision as of 06:45, 8 October 2014
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4umu is ON HOLD	+	The entry 4umu 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 "4umu" [edit=sysop:move=sysop]

OCA — Wed, 28 May 2014 08:37:26 GMT

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

←Older revision

Revision as of 08:37, 28 May 2014

OCA: New page: '''Unreleased structure''' The entry 4umu is ON HOLD Authors: Johnson, C.N., Berdini, V., Beke, L., Bonnet, P., Brehmer, D., Coyle, J.E., Day, P.J., Frederickson, M., Freyne, E.J.E., Gi...

OCA — Wed, 28 May 2014 08:37:24 GMT

New page: '''Unreleased structure''' The entry 4umu is ON HOLD Authors: Johnson, C.N., Berdini, V., Beke, L., Bonnet, P., Brehmer, D., Coyle, J.E., Day, P.J., Frederickson, M., Freyne, E.J.E., Gi...

New page

'''Unreleased structure'''

The entry 4umu is ON HOLD

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