4d2p: Difference between revisions

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==Structure of MELK in complex with inhibitors==
==Structure of MELK in complex with inhibitors==
<StructureSection load='4d2p' size='340' side='right' caption='[[4d2p]], [[Resolution|resolution]] 2.55&Aring;' scene=''>
<StructureSection load='4d2p' size='340' side='right'caption='[[4d2p]], [[Resolution|resolution]] 2.55&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4d2p]] 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=4D2P OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4D2P FirstGlance]. <br>
<table><tr><td colspan='2'>[[4d2p]] 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=4D2P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4D2P FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6Z7:7-({4-[(3-HYDROXY-5-METHOXYPHENYL)AMINO]BENZOYL}AMINO)-1,2,3,4-TETRAHYDROISOQUINOLINIUM'>6Z7</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]] 2.55&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4d2t|4d2t]], [[4d2v|4d2v]], [[4d2w|4d2w]]</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6Z7:7-({4-[(3-HYDROXY-5-METHOXYPHENYL)AMINO]BENZOYL}AMINO)-1,2,3,4-TETRAHYDROISOQUINOLINIUM'>6Z7</scene></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </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=4d2p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4d2p OCA], [https://pdbe.org/4d2p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4d2p RCSB], [https://www.ebi.ac.uk/pdbsum/4d2p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4d2p 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=4d2p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4d2p OCA], [http://pdbe.org/4d2p PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4d2p RCSB], [http://www.ebi.ac.uk/pdbsum/4d2p PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4d2p 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 ==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Non-specific serine/threonine protein kinase]]
[[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 sterbased drug design]]
[[Category: Kinase]]
[[Category: Transferase]]

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