View source for 8e90


==Inhibition of Human Menin by SNDX-5613==
<StructureSection load='8e90' size='340' side='right'caption='[[8e90]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8e90]] 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=8E90 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8E90 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]] 1.85&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=OQ4:2-({4-[7-({(1r,4r)-4-[(ethanesulfonyl)amino]cyclohexyl}methyl)-2,7-diazaspiro[3.5]nonan-2-yl]pyrimidin-5-yl}oxy)-N-ethyl-5-fluoro-N-(propan-2-yl)benzamide'>OQ4</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=8e90 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8e90 OCA], [https://pdbe.org/8e90 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8e90 RCSB], [https://www.ebi.ac.uk/pdbsum/8e90 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8e90 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/MEN1_HUMAN MEN1_HUMAN] Defects in MEN1 are the cause of familial multiple endocrine neoplasia type I (MEN1) [MIM:[https://omim.org/entry/131100 131100]. Autosomal dominant disorder characterized by tumors of the parathyroid glands, gastro-intestinal endocrine tissue, the anterior pituitary and other tissues. Cutaneous lesions and nervous-tissue tumors can exist. Prognosis in MEN1 patients is related to hormonal hypersecretion by tumors, such as hypergastrinemia causing severe peptic ulcer disease (Zollinger-Ellison syndrome, ZES), primary hyperparathyroidism, and acute forms of hyperinsulinemia.<ref>PMID:14992727</ref> <ref>PMID:9989505</ref> <ref>PMID:9103196</ref> <ref>PMID:17555499</ref> <ref>PMID:9215689</ref> <ref>PMID:9215690</ref> <ref>PMID:9463336</ref> <ref>PMID:9683585</ref> <ref>PMID:9820618</ref> <ref>PMID:9671267</ref> <ref>PMID:10660339</ref> <ref>PMID:9506756</ref> <ref>PMID:9709921</ref> <ref>PMID:9709976</ref> <ref>PMID:9709985</ref> <ref>PMID:9740255</ref> <ref>PMID:9747036</ref> <ref>PMID:9832038</ref> <ref>PMID:10617276</ref> <ref>PMID:10229909</ref> <ref>PMID:10576763</ref> <ref>PMID:9888389</ref> <ref>PMID:10090472</ref> <ref>PMID:10534569</ref> <ref>PMID:10993647</ref> <ref>PMID:10849016</ref> <ref>PMID:10664520</ref> <ref>PMID:11102994</ref> <ref>PMID:11134142</ref> <ref>PMID:11241849</ref> <ref>PMID:12112656</ref> <ref>PMID:12417605</ref> <ref>PMID:12050235</ref> <ref>PMID:12699448</ref> <ref>PMID:12791038</ref> <ref>PMID:12652570</ref> <ref>PMID:14686752</ref> <ref>PMID:12746426</ref> <ref>PMID:15730416</ref> <ref>PMID:15714081</ref>   Defects in MEN1 are the cause of familial isolated hyperparathyroidism (FIHP) [MIM:[https://omim.org/entry/145000 145000]; also known as hyperparathyroidism type 1 (HRPT1). FIHP is an autosomal dominant disorder characterized by hypercalcemia, elevated parathyroid hormone (PTH) levels, and uniglandular or multiglandular parathyroid tumors.<ref>PMID:9888389</ref> <ref>PMID:12699448</ref> <ref>PMID:9792884</ref> <ref>PMID:9843042</ref> <ref>PMID:10664521</ref> <ref>PMID:10634381</ref> <ref>PMID:12016470</ref> 
== Function ==
[https://www.uniprot.org/uniprot/MEN1_HUMAN MEN1_HUMAN] Essential component of a MLL/SET1 histone methyltransferase (HMT) complex, a complex that specifically methylates 'Lys-4' of histone H3 (H3K4). Functions as a transcriptional regulator. Binds to the TERT promoter and represses telomerase expression. Plays a role in TGFB1-mediated inhibition of cell-proliferation, possibly regulating SMAD3 transcriptional activity. Represses JUND-mediated transcriptional activation on AP1 sites, as well as that mediated by NFKB subunit RELA. Positively regulates HOXC8 and HOXC6 gene expression. May be involved in normal hematopoiesis through the activation of HOXA9 expression (By similarity). May be involved in DNA repair.<ref>PMID:11526476</ref> <ref>PMID:11274402</ref> <ref>PMID:12874027</ref> <ref>PMID:12837246</ref> <ref>PMID:14992727</ref> 

==See Also==
*[[Menin|Menin]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: KULKARNI S]]
[[Category: McGeehan GM]]
[[Category: McKeever BM]]