4bkz - Revision history

OCA at 11:53, 20 December 2023

2023-12-20T11:53:33Z

←Older revision		Revision as of 11:53, 20 December 2023
Line 3:		Line 3:
	<StructureSection load='4bkz' size='340' side='right'caption='[[4bkz]], [[Resolution\|resolution]] 2.20Å' scene=''>		<StructureSection load='4bkz' size='340' side='right'caption='[[4bkz]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4bkz]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BKZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BKZ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4bkz]] 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=4BKZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BKZ FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=1WS:N-(3-AMINOPROPYL)-8~~-[~~(3-FLUOROPHENYL)AMINO~~]-2~~,4,5,7-TETRAHYDROPYRAZOLO[3,4-E]INDAZOLE-3-CARBOXAMIDE'>1WS</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]] 2.2Å</td></tr>
-	<tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat"><~~div style~~='~~overflow~~: ~~auto; max~~-~~height: 3em;'>~~[~~[4bky\|4bky]~~], [~~[4bl1\|4bl1]~~]</~~div~~></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1WS:N-(3-AMINOPROPYL)-8-[(3-FLUOROPHENYL)AMINO]-2,4,5,7-TETRAHYDROPYRAZOLO[3,4-E]INDAZOLE-3-CARBOXAMIDE'>1WS</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=4bkz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bkz OCA], [https://pdbe.org/4bkz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4bkz RCSB], [https://www.ebi.ac.uk/pdbsum/4bkz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4bkz 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=4bkz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bkz OCA], [https://pdbe.org/4bkz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4bkz RCSB], [https://www.ebi.ac.uk/pdbsum/4bkz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4bkz 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 ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Bertrand~~, J A~~]]	+	[[Category: Bertrand JA]]
-	[[Category: Canevari, G]]	+	[[Category: Canevari G]]
-	[[Category: Carpinelli, P]]	+	[[Category: Carpinelli P]]
-	[[Category: Cucchi, U]]	+	[[Category: Cucchi U]]
-	~~[[Category: Depaolini, S Re~~]]	+	[[Category: Forte B]]
-	[[Category: Forte, B]]	+	[[Category: Re Depaolini S]]
-	[[Category: ~~Transferase~~]]	+

OCA at 07:17, 31 August 2022

2022-08-31T07:17:08Z

OCA at 13:27, 13 March 2019

2019-03-13T13:27:33Z

←Older revision		Revision as of 13:27, 13 March 2019
Line 1:		Line 1:

	==Crystal structure of unphosphorylated Maternal Embryonic Leucine zipper Kinase (MELK) in complex with a benzodipyrazole inhibitor==		==Crystal structure of unphosphorylated Maternal Embryonic Leucine zipper Kinase (MELK) in complex with a benzodipyrazole inhibitor==
-	<StructureSection load='4bkz' size='340' side='right' caption='[[4bkz]], [[Resolution\|resolution]] 2.20Å' scene=''>	+	<StructureSection load='4bkz' size='340' side='right'caption='[[4bkz]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4bkz]] 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=4BKZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BKZ FirstGlance]. <br>		<table><tr><td colspan='2'>[[4bkz]] 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=4BKZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BKZ FirstGlance]. <br>
Line 26:		Line 26:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Bertrand, J A]]		[[Category: Bertrand, J A]]
	[[Category: Canevari, G]]		[[Category: Canevari, G]]

OCA at 01:52, 5 August 2016

2016-08-05T01:52:47Z

←Older revision		Revision as of 01:52, 5 August 2016
Line 1:		Line 1:
		+
	==Crystal structure of unphosphorylated Maternal Embryonic Leucine zipper Kinase (MELK) in complex with a benzodipyrazole inhibitor==		==Crystal structure of unphosphorylated Maternal Embryonic Leucine zipper Kinase (MELK) in complex with a benzodipyrazole inhibitor==
	<StructureSection load='4bkz' size='340' side='right' caption='[[4bkz]], [[Resolution\|resolution]] 2.20Å' scene=''>		<StructureSection load='4bkz' size='340' side='right' caption='[[4bkz]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4bkz]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BKZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BKZ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4bkz]] 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=4BKZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BKZ FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1WS:N-(3-AMINOPROPYL)-8-[(3-FLUOROPHENYL)AMINO]-2,4,5,7-TETRAHYDROPYRAZOLO[3,4-E]INDAZOLE-3-CARBOXAMIDE'>1WS</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1WS:N-(3-AMINOPROPYL)-8-[(3-FLUOROPHENYL)AMINO]-2,4,5,7-TETRAHYDROPYRAZOLO[3,4-E]INDAZOLE-3-CARBOXAMIDE'>1WS</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4bky\|4bky]], [[4bl1\|4bl1]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4bky\|4bky]], [[4bl1\|4bl1]]</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=4bkz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bkz OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4bkz RCSB], [http://www.ebi.ac.uk/pdbsum/4bkz 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=4bkz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bkz OCA], [http://pdbe.org/4bkz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4bkz RCSB], [http://www.ebi.ac.uk/pdbsum/4bkz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4bkz 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 4bkz" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Bertrand, J A]]		[[Category: Bertrand, J A]]
	[[Category: Canevari, G]]		[[Category: Canevari, G]]

OCA at 09:32, 21 December 2014

2014-12-21T09:32:52Z

←Older revision		Revision as of 09:32, 21 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_4bkz\| PDB=4bkz \| SCENE= }}~~	+	==Crystal structure of unphosphorylated Maternal Embryonic Leucine zipper Kinase (MELK) in complex with a benzodipyrazole inhibitor==
-	===Crystal structure of unphosphorylated Maternal Embryonic Leucine zipper Kinase (MELK) in complex with a benzodipyrazole inhibitor===	+	<StructureSection load='4bkz' size='340' side='right' caption='[[4bkz]], [[Resolution\|resolution]] 2.20Å' scene=''>
-	~~{{ABSTRACT_PUBMED_23914841}}~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[4bkz]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BKZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BKZ FirstGlance]. <br>
-	==Disease==	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1WS:N-(3-AMINOPROPYL)-8-[(3-FLUOROPHENYL)AMINO]-2,4,5,7-TETRAHYDROPYRAZOLO[3,4-E]INDAZOLE-3-CARBOXAMIDE'>1WS</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4bky\|4bky]], [[4bl1\|4bl1]]</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=4bkz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bkz OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4bkz RCSB], [http://www.ebi.ac.uk/pdbsum/4bkz 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.		[[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 ==
-	==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 ==
		+	Maternal Embryonic Leucine zipper Kinase (MELK) is upregulated in several types of tumor, including breast, prostate and brain tumors. Its expression is generally associated with cell survival, cell proliferation and resistance to apoptosis. Therefore, the potential of MELK inhibitors as therapeutic agents is recently attracting considerable interest. Here we report the first structures of MELK in complex with AMP-PNP and with nanomolar inhibitors. Our studies shed some light on the role of MELK UBA domain, provide a characterization of the kinase active site and identify key residues for achieving high potency, laying the groundwork for structure-based drug design efforts.

-	~~==About this Structure==~~	+	Structural insight into Maternal Embryonic Leucine zipper Kinase (MELK) conformation and inhibition towards structure-based drug design.,Canevari G, Re Depaolini S, Cucchi U, Bertrand JA, Casale E, Perrera C, Forte B, Carpinelli P, Felder ER Biochemistry. 2013 Aug 5. PMID:23914841<ref>PMID:23914841</ref>
-	~~[[4bkz]] is a 1 chain~~ structure ~~with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Homo_sapiens Homo sapiens]~~. ~~Full crystallographic information is available from [http~~:/~~/oca.weizmann.ac.il/oca-bin/ocashort?id=4BKZ OCA].~~	+

-	==~~Reference~~==	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~<ref group="xtra">PMID:023914841</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	</div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Bertrand, J A.]]	+	[[Category: Bertrand, J A]]
-	[[Category: Canevari, G.]]	+	[[Category: Canevari, G]]
-	[[Category: Carpinelli, P.]]	+	[[Category: Carpinelli, P]]
-	[[Category: Cucchi, U.]]	+	[[Category: Cucchi, U]]
-	[[Category: Depaolini, S Re.]]	+	[[Category: Depaolini, S Re]]
-	[[Category: Forte, B.]]	+	[[Category: Forte, B]]
	[[Category: Transferase]]		[[Category: Transferase]]

OCA at 08:29, 21 August 2013

2013-08-21T08:29:06Z

←Older revision		Revision as of 08:29, 21 August 2013
Line 1:		Line 1:
-	~~'''Unreleased~~ structure~~'''~~	+	{{STRUCTURE_4bkz\| PDB=4bkz \| SCENE= }}
		+	===Crystal structure of unphosphorylated Maternal Embryonic Leucine zipper Kinase (MELK) in complex with a benzodipyrazole inhibitor===
		+	{{ABSTRACT_PUBMED_23914841}}

-	~~The entry 4bkz~~ is ~~ON HOLD until Paper Publication~~	+	==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.

-	~~Authors~~: ~~Canevari, G~~., ~~Re Depaolini~~, S., ~~Cucchi~~, U., ~~Forte~~, B., ~~Carpinelli, P~~., ~~Bertrand, J~~.A.	+	==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>

-	~~Description: Crystal~~ structure ~~of unphosphorylated Maternal Embryonic Leucine zipper Kinase (MELK) in complex~~ with ~~a benzodipyrazole inhibitor~~	+	==About this Structure==
		+	[[4bkz]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BKZ OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:023914841</ref><references group="xtra"/><references/>
		+	[[Category: Homo sapiens]]
		+	[[Category: Bertrand, J A.]]
		+	[[Category: Canevari, G.]]
		+	[[Category: Carpinelli, P.]]
		+	[[Category: Cucchi, U.]]
		+	[[Category: Depaolini, S Re.]]
		+	[[Category: Forte, B.]]
		+	[[Category: Transferase]]

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

2013-05-08T07:06:04Z

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

←Older revision

Revision as of 07:06, 8 May 2013

OCA: New page: '''Unreleased structure''' The entry 4bkz is ON HOLD until Paper Publication Authors: Canevari, G., Re Depaolini, S., Cucchi, U., Forte, B., Carpinelli, P., Bertrand, J.A. Description:...

2013-05-08T07:06:03Z

New page: '''Unreleased structure''' The entry 4bkz is ON HOLD until Paper Publication Authors: Canevari, G., Re Depaolini, S., Cucchi, U., Forte, B., Carpinelli, P., Bertrand, J.A. Description:...

New page

'''Unreleased structure'''

The entry 4bkz is ON HOLD until Paper Publication

Authors: Canevari, G., Re Depaolini, S., Cucchi, U., Forte, B., Carpinelli, P., Bertrand, J.A.

Description: Crystal structure of unphosphorylated Maternal Embryonic Leucine zipper Kinase (MELK) in complex with a benzodipyrazole inhibitor

←Older revision		Revision as of 07:17, 31 August 2022
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	<StructureSection load='4bkz' size='340' side='right'caption='[[4bkz]], [[Resolution\|resolution]] 2.20Å' scene=''>		<StructureSection load='4bkz' size='340' side='right'caption='[[4bkz]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4bkz]] 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=4BKZ OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4BKZ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4bkz]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BKZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BKZ FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1WS:N-(3-AMINOPROPYL)-8-[(3-FLUOROPHENYL)AMINO]-2,4,5,7-TETRAHYDROPYRAZOLO[3,4-E]INDAZOLE-3-CARBOXAMIDE'>1WS</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1WS:N-(3-AMINOPROPYL)-8-[(3-FLUOROPHENYL)AMINO]-2,4,5,7-TETRAHYDROPYRAZOLO[3,4-E]INDAZOLE-3-CARBOXAMIDE'>1WS</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4bky\|4bky]], [[4bl1\|4bl1]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[4bky\|4bky]], [[4bl1\|4bl1]]</div></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=4bkz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bkz OCA], [~~http~~://pdbe.org/4bkz PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4bkz RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4bkz PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4bkz 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=4bkz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bkz OCA], [https://pdbe.org/4bkz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4bkz RCSB], [https://www.ebi.ac.uk/pdbsum/4bkz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4bkz 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 ==