4cqg

From Proteopedia

(Difference between revisions)

Revision as of 07:27, 24 April 2019

The crystal structure of MPK38 in complex with OTSSP167, an orally- administrative MELK selective inhibitor

Structural highlights

4cqg is a 1 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Gene:	Melk, Kiaa0175, Pk38 (LK3 transgenic mice)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[MELK_MOUSE] 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. Required for proliferation of embryonic and postnatal multipotent neural progenitors. Phosphorylates and inhibits 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]

Publication Abstract from PubMed

Murine protein serine/threonine kinase 38 (MPK38), also known as maternal embryonic leucine zipper kinase (MELK), has been associated with various human cancers and plays an important role in the formation of cancer stem cells. OTSSP167, a MELK selective inhibitor, exhibits a strong in vitro activity, conferring an IC50 of 0.41nM and in vivo effect on various human cancer xenograft models. Here, we report the crystal structure of MPK38 (T167E), an active mutant, in complex with OTSSP167 and describe its detailed protein-inhibitor interactions. Comparison with the previous determined structure of MELK bound to the nanomolar inhibitors shows that OTSSP167 effectively fits into the active site, thus offering an opportunity for structure-based development and optimization of MELK inhibitors.

The crystal structure of MPK38 in complex with OTSSP167, an orally administrative MELK selective inhibitor.,Cho YS, Kang Y, Kim K, Cha YJ, Cho HS Biochem Biophys Res Commun. 2014 Apr 25;447(1):7-11. doi:, 10.1016/j.bbrc.2014.03.034. Epub 2014 Mar 18. PMID:24657156^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Nakano I, Paucar AA, Bajpai R, Dougherty JD, Zewail A, Kelly TK, Kim KJ, Ou J, Groszer M, Imura T, Freije WA, Nelson SF, Sofroniew MV, Wu H, Liu X, Terskikh AV, Geschwind DH, Kornblum HI. Maternal embryonic leucine zipper kinase (MELK) regulates multipotent neural progenitor proliferation. J Cell Biol. 2005 Aug 1;170(3):413-27. PMID:16061694 doi:http://dx.doi.org/10.1083/jcb.200412115
↑ Jung H, Seong HA, Ha H. Murine protein serine/threonine kinase 38 activates apoptosis signal-regulating kinase 1 via Thr 838 phosphorylation. J Biol Chem. 2008 Dec 12;283(50):34541-53. doi: 10.1074/jbc.M807219200. Epub 2008, Oct 23. PMID:18948261 doi:http://dx.doi.org/10.1074/jbc.M807219200
↑ Cho YS, Kang Y, Kim K, Cha YJ, Cho HS. The crystal structure of MPK38 in complex with OTSSP167, an orally administrative MELK selective inhibitor. Biochem Biophys Res Commun. 2014 Apr 25;447(1):7-11. doi:, 10.1016/j.bbrc.2014.03.034. Epub 2014 Mar 18. PMID:24657156 doi:http://dx.doi.org/10.1016/j.bbrc.2014.03.034

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4cqg"

@@ Line 3: / Line 3: @@
 <StructureSection load='4cqg' size='340' side='right'caption='[[4cqg]], [[Resolution|resolution]] 2.57&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4cqg]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CQG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4CQG FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4cqg]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CQG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4CQG FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=OT5:1-[6-(3,5-DICHLORO-4-HYDROXYPHENYL)-4-({TRANS-4-[(DIMETHYLAMINO)METHYL]CYCLOHEXYL}AMINO)-1,5-NAPHTHYRIDIN-3-YL]ETHANONE'>OT5</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Melk, Kiaa0175, Pk38 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=4cqg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cqg OCA], [http://pdbe.org/4cqg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4cqg RCSB], [http://www.ebi.ac.uk/pdbsum/4cqg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4cqg ProSAT]</span></td></tr>
 </table>
@@ Line 23: / Line 24: @@
 </StructureSection>
 [[Category: Large Structures]]
+[[Category: Lk3 transgenic mice]]
 [[Category: Cho, H S]]
 [[Category: Cho, Y S]]
 [[Category: Kang, Y J]]
 [[Category: Transferase]]

4cqg

From Proteopedia

Revision as of 07:27, 24 April 2019

The crystal structure of MPK38 in complex with OTSSP167, an orally- administrative MELK selective inhibitor

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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