View source for 6hkm


==Crystal structure of Compound 1 with ERK5==
<StructureSection load='6hkm' size='340' side='right' caption='[[6hkm]], [[Resolution|resolution]] 2.47&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6hkm]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HKM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HKM FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=G92:[4-(6,7-dimethoxyquinazolin-4-yl)piperidin-1-yl]-[4-(trifluoromethyloxy)phenyl]methanone'>G92</scene></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase Mitogen-activated protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.24 2.7.11.24] </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=6hkm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hkm OCA], [http://pdbe.org/6hkm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6hkm RCSB], [http://www.ebi.ac.uk/pdbsum/6hkm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6hkm ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/MK07_HUMAN MK07_HUMAN]] Plays a role in various cellular processes such as proliferation, differentiation and cell survival. The upstream activator of MAPK7 is the MAPK kinase MAP2K5. Upon activation, it translocates to the nucleus and phosphorylates various downstream targets including MEF2C. EGF activates MAPK7 through a Ras-independent and MAP2K5-dependent pathway. May have a role in muscle cell differentiation. May be important for endothelial function and maintenance of blood vessel integrity. MAP2K5 and MAPK7 interact specifically with one another and not with MEK1/ERK1 or MEK2/ERK2 pathways. Phosphorylates SGK1 at Ser-78 and this is required for growth factor-induced cell cycle progression. Involved in the regulation of p53/TP53 by disrupting the PML-MDM2 interaction.<ref>PMID:9384584</ref> <ref>PMID:9790194</ref> <ref>PMID:11254654</ref> <ref>PMID:11278431</ref> <ref>PMID:22869143</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The availability of a chemical probe to study the role of a specific domain of a protein in a concentration- and time-dependent manner is of high value. Herein, we report the identification of a highly potent and selective ERK5 inhibitor BAY-885 by high-throughput screening and subsequent structure-based optimization. ERK5 is a key integrator of cellular signal transduction, and it has been shown to play a role in various cellular processes such as proliferation, differentiation, apoptosis, and cell survival. We could demonstrate that inhibition of ERK5 kinase and transcriptional activity with a small molecule did not translate into antiproliferative activity in different relevant cell models, which is in contrast to the results obtained by RNAi technology.

Discovery and Characterization of the Potent and Highly Selective (Piperidin-4-yl)pyrido[3,2- d]pyrimidine Based in Vitro Probe BAY-885 for the Kinase ERK5.,Nguyen D, Lemos C, Wortmann L, Eis K, Holton SJ, Boemer U, Moosmayer D, Eberspaecher U, Weiske J, Lechner C, Prechtl S, Suelzle D, Siegel F, Prinz F, Lesche R, Nicke B, Nowak-Reppel K, Himmel H, Mumberg D, von Nussbaum F, Nising CF, Bauser M, Haegebarth A J Med Chem. 2019 Jan 24;62(2):928-940. doi: 10.1021/acs.jmedchem.8b01606. Epub, 2019 Jan 9. PMID:30563338<ref>PMID:30563338</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6hkm" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Mitogen-activated protein kinase]]
[[Category: Bauser, M]]
[[Category: Boemer, U]]
[[Category: Eis, K]]
[[Category: Haegebarth, A]]
[[Category: Holton, S J]]
[[Category: Lechner, C]]
[[Category: Lemos, C]]
[[Category: Lesche, R]]
[[Category: Mumberg, D]]
[[Category: Nguyen, D]]
[[Category: Nicke, B]]
[[Category: Prechtl, S]]
[[Category: Prinz, F]]
[[Category: Siegel, F]]
[[Category: Suelze, D]]
[[Category: Wortmann, L]]
[[Category: Erk5 kinase]]
[[Category: Immune system]]
[[Category: Transferase]]