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==Crystal structure of unphosphorylated Maternal Embryonic Leucine zipper Kinase (MELK) in complex with AMP-PNP==
==Crystal structure of unphosphorylated Maternal Embryonic Leucine zipper Kinase (MELK) in complex with AMP-PNP==
<StructureSection load='4bl1' size='340' side='right' caption='[[4bl1]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
<StructureSection load='4bl1' size='340' side='right' caption='[[4bl1]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4bl1]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3zgw 3zgw]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BL1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BL1 FirstGlance]. <br>
<table><tr><td colspan='2'>[[4bl1]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3zgw 3zgw]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BL1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BL1 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene></td></tr>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4bky|4bky]], [[4bkz|4bkz]]</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4bky|4bky]], [[4bkz|4bkz]]</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=4bl1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bl1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4bl1 RCSB], [http://www.ebi.ac.uk/pdbsum/4bl1 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=4bl1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bl1 OCA], [http://pdbe.org/4bl1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4bl1 RCSB], [http://www.ebi.ac.uk/pdbsum/4bl1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4bl1 ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Human]]
[[Category: Bertrand, J A]]
[[Category: Bertrand, J A]]
[[Category: Canevari, G]]
[[Category: Canevari, G]]

Revision as of 19:20, 5 August 2016

Crystal structure of unphosphorylated Maternal Embryonic Leucine zipper Kinase (MELK) in complex with AMP-PNPCrystal structure of unphosphorylated Maternal Embryonic Leucine zipper Kinase (MELK) in complex with AMP-PNP

Structural highlights

4bl1 is a 1 chain structure with sequence from Human. This structure supersedes the now removed PDB entry 3zgw. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[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

[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.[1] [2] [3] [4] [5] [6]

References

  1. ↑ Seong HA, Gil M, Kim KT, Kim SJ, Ha H. Phosphorylation of a novel zinc-finger-like protein, ZPR9, by murine protein serine/threonine kinase 38 (MPK38). Biochem J. 2002 Feb 1;361(Pt 3):597-604. PMID:11802789
  2. ↑ Davezac N, Baldin V, Blot J, Ducommun B, Tassan JP. Human pEg3 kinase associates with and phosphorylates CDC25B phosphatase: a potential role for pEg3 in cell cycle regulation. Oncogene. 2002 Oct 31;21(50):7630-41. PMID:12400006 doi:10.1038/sj.onc.1205870
  3. ↑ Vulsteke V, Beullens M, Boudrez A, Keppens S, Van Eynde A, Rider MH, Stalmans W, Bollen M. Inhibition of spliceosome assembly by the cell cycle-regulated protein kinase MELK and involvement of splicing factor NIPP1. J Biol Chem. 2004 Mar 5;279(10):8642-7. Epub 2003 Dec 29. PMID:14699119 doi:10.1074/jbc.M311466200
  4. ↑ Mirey G, Chartrain I, Froment C, Quaranta M, Bouche JP, Monsarrat B, Tassan JP, Ducommun B. CDC25B phosphorylated by pEg3 localizes to the centrosome and the spindle poles at mitosis. Cell Cycle. 2005 Jun;4(6):806-11. Epub 2005 Jun 5. PMID:15908796
  5. ↑ Beullens M, Vancauwenbergh S, Morrice N, Derua R, Ceulemans H, Waelkens E, Bollen M. Substrate specificity and activity regulation of protein kinase MELK. J Biol Chem. 2005 Dec 2;280(48):40003-11. Epub 2005 Oct 10. PMID:16216881 doi:10.1074/jbc.M507274200
  6. ↑ Lin ML, Park JH, Nishidate T, Nakamura Y, Katagiri T. Involvement of maternal embryonic leucine zipper kinase (MELK) in mammary carcinogenesis through interaction with Bcl-G, a pro-apoptotic member of the Bcl-2 family. Breast Cancer Res. 2007;9(1):R17. PMID:17280616 doi:10.1186/bcr1650

4bl1, resolution 2.60Å

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