View source for 9qad


==Crystal structure of the SMARCA2 bromodomain bound to a tricyclic pyrimidoindolone inhibitor (compound 17)==
<StructureSection load='9qad' size='340' side='right'caption='[[9qad]], [[Resolution|resolution]] 2.08&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9qad]] is a 3 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=9QAD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9QAD 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]] 2.08&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1I45:5-oxidanyl-2-(phenylmethyl)-1,9-dihydropyrimido[4,5-b]indol-4-one'>A1I45</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=9qad FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9qad OCA], [https://pdbe.org/9qad PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9qad RCSB], [https://www.ebi.ac.uk/pdbsum/9qad PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9qad ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/SMCA2_HUMAN SMCA2_HUMAN] Defects in SMARCA2 are the cause of Nicolaides-Baraitser syndrome (NCBRS) [MIM:[https://omim.org/entry/601358 601358]. A rare disorder characterized by severe mental retardation with absent or limited speech, seizures, short stature, sparse hair, typical facial characteristics, brachydactyly, prominent finger joints and broad distal phalanges. Some of the features are progressive with time.<ref>PMID:22426308</ref> <ref>PMID:22366787</ref> 
== Function ==
[https://www.uniprot.org/uniprot/SMCA2_HUMAN SMCA2_HUMAN] Transcriptional coactivator cooperating with nuclear hormone receptors to potentiate transcriptional activation. Also involved in vitamin D-coupled transcription regulation via its association with the WINAC complex, a chromatin-remodeling complex recruited by vitamin D receptor (VDR), which is required for the ligand-bound VDR-mediated transrepression of the CYP27B1 gene. Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and the neuron-specific chromatin remodeling complex (nBAF complex). During neural development a switch from a stem/progenitor to a post-mitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to post-mitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth (By similarity).<ref>PMID:12837248</ref> 
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Schimpl M]]