View source for 8paw


==Crystal structure of MST1 with a MAP4K1 SMOL inhibitor==
<StructureSection load='8paw' size='340' side='right'caption='[[8paw]], [[Resolution|resolution]] 2.14&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8paw]] is a 2 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=8PAW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8PAW FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.14&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ASP:ASPARTIC+ACID'>ASP</scene>, <scene name='pdbligand=CXS:3-CYCLOHEXYL-1-PROPYLSULFONIC+ACID'>CXS</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene>, <scene name='pdbligand=XQL:1-[3,5-bis(fluoranyl)-4-[[3-(1-propan-2-ylpyrazol-3-yl)-1~{H}-pyrrolo[2,3-b]pyridin-4-yl]oxy]phenyl]-3-(2-methoxyethyl)urea'>XQL</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=8paw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8paw OCA], [https://pdbe.org/8paw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8paw RCSB], [https://www.ebi.ac.uk/pdbsum/8paw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8paw ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/STK4_HUMAN STK4_HUMAN] Stress-activated, pro-apoptotic kinase which, following caspase-cleavage, enters the nucleus and induces chromatin condensation followed by internucleosomal DNA fragmentation. Key component of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. STK3/MST2 and STK4/MST1 are required to repress proliferation of mature hepatocytes, to prevent activation of facultative adult liver stem cells (oval cells), and to inhibit tumor formation (By similarity). Phosphorylates 'Ser-14' of histone H2B (H2BS14ph) during apoptosis. Phosphorylates FOXO3 upon oxidative stress, which results in its nuclear translocation and cell death initiation. Phosphorylates MOBKL1A, MOBKL1B and RASSF2. Phosphorylates TNNI3 (cardiac Tn-I) and alters its binding affinity to TNNC1 (cardiac Tn-C) and TNNT2 (cardiac Tn-T). Phosphorylates FOXO1 on 'Ser-212' and regulates its activation and stimulates transcription of PMAIP1 in a FOXO1-dependent manner. Phosphorylates SIRT1 and inhibits SIRT1-mediated p53/TP53 deacetylation, thereby promoting p53/TP53 dependent transcription and apoptosis upon DNA damage. Acts as an inhibitor of PKB/AKT1. Phosphorylates AR on 'Ser-650' and suppresses its activity by intersecting with PKB/AKT1 signaling and antagonizing formation of AR-chromatin complexes.<ref>PMID:8816758</ref> <ref>PMID:8702870</ref> <ref>PMID:11278283</ref> <ref>PMID:11517310</ref> <ref>PMID:12757711</ref> <ref>PMID:15109305</ref> <ref>PMID:16510573</ref> <ref>PMID:16751106</ref> <ref>PMID:16930133</ref> <ref>PMID:17932490</ref> <ref>PMID:18328708</ref> <ref>PMID:18986304</ref> <ref>PMID:19525978</ref> <ref>PMID:21245099</ref> <ref>PMID:21512132</ref> <ref>PMID:21212262</ref> 
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Friberg A]]