5dkh: Difference between revisions

Latest revision as of 00:46, 29 June 2023

Crystal structure of the bromodomain of human BRM (SMARCA2) in complex with a hydroxyphenyl propenone inhibitor 17Crystal structure of the bromodomain of human BRM (SMARCA2) in complex with a hydroxyphenyl propenone inhibitor 17

Structural highlights

5dkh is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.7Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

SMCA2_HUMAN Defects in SMARCA2 are the cause of Nicolaides-Baraitser syndrome (NCBRS) [MIM: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.^[1] ^[2]

Function

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).^[3]

References

↑ Tsurusaki Y, Okamoto N, Ohashi H, Kosho T, Imai Y, Hibi-Ko Y, Kaname T, Naritomi K, Kawame H, Wakui K, Fukushima Y, Homma T, Kato M, Hiraki Y, Yamagata T, Yano S, Mizuno S, Sakazume S, Ishii T, Nagai T, Shiina M, Ogata K, Ohta T, Niikawa N, Miyatake S, Okada I, Mizuguchi T, Doi H, Saitsu H, Miyake N, Matsumoto N. Mutations affecting components of the SWI/SNF complex cause Coffin-Siris syndrome. Nat Genet. 2012 Mar 18;44(4):376-8. doi: 10.1038/ng.2219. PMID:22426308 doi:10.1038/ng.2219
↑ Van Houdt JK, Nowakowska BA, Sousa SB, van Schaik BD, Seuntjens E, Avonce N, Sifrim A, Abdul-Rahman OA, van den Boogaard MJ, Bottani A, Castori M, Cormier-Daire V, Deardorff MA, Filges I, Fryer A, Fryns JP, Gana S, Garavelli L, Gillessen-Kaesbach G, Hall BD, Horn D, Huylebroeck D, Klapecki J, Krajewska-Walasek M, Kuechler A, Lines MA, Maas S, Macdermot KD, McKee S, Magee A, de Man SA, Moreau Y, Morice-Picard F, Obersztyn E, Pilch J, Rosser E, Shannon N, Stolte-Dijkstra I, Van Dijck P, Vilain C, Vogels A, Wakeling E, Wieczorek D, Wilson L, Zuffardi O, van Kampen AH, Devriendt K, Hennekam R, Vermeesch JR. Heterozygous missense mutations in SMARCA2 cause Nicolaides-Baraitser syndrome. Nat Genet. 2012 Feb 26;44(4):445-9, S1. doi: 10.1038/ng.1105. PMID:22366787 doi:10.1038/ng.1105
↑ Kitagawa H, Fujiki R, Yoshimura K, Mezaki Y, Uematsu Y, Matsui D, Ogawa S, Unno K, Okubo M, Tokita A, Nakagawa T, Ito T, Ishimi Y, Nagasawa H, Matsumoto T, Yanagisawa J, Kato S. The chromatin-remodeling complex WINAC targets a nuclear receptor to promoters and is impaired in Williams syndrome. Cell. 2003 Jun 27;113(7):905-17. PMID:12837248

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OCA

[1] Tsurusaki Y, Okamoto N, Ohashi H, Kosho T, Imai Y, Hibi-Ko Y, Kaname T, Naritomi K, Kawame H, Wakui K, Fukushima Y, Homma T, Kato M, Hiraki Y, Yamagata T, Yano S, Mizuno S, Sakazume S, Ishii T, Nagai T, Shiina M, Ogata K, Ohta T, Niikawa N, Miyatake S, Okada I, Mizuguchi T, Doi H, Saitsu H, Miyake N, Matsumoto N. Mutations affecting components of the SWI/SNF complex cause Coffin-Siris syndrome. Nat Genet. 2012 Mar 18;44(4):376-8. doi: 10.1038/ng.2219. PMID:22426308 doi:10.1038/ng.2219

[2] Van Houdt JK, Nowakowska BA, Sousa SB, van Schaik BD, Seuntjens E, Avonce N, Sifrim A, Abdul-Rahman OA, van den Boogaard MJ, Bottani A, Castori M, Cormier-Daire V, Deardorff MA, Filges I, Fryer A, Fryns JP, Gana S, Garavelli L, Gillessen-Kaesbach G, Hall BD, Horn D, Huylebroeck D, Klapecki J, Krajewska-Walasek M, Kuechler A, Lines MA, Maas S, Macdermot KD, McKee S, Magee A, de Man SA, Moreau Y, Morice-Picard F, Obersztyn E, Pilch J, Rosser E, Shannon N, Stolte-Dijkstra I, Van Dijck P, Vilain C, Vogels A, Wakeling E, Wieczorek D, Wilson L, Zuffardi O, van Kampen AH, Devriendt K, Hennekam R, Vermeesch JR. Heterozygous missense mutations in SMARCA2 cause Nicolaides-Baraitser syndrome. Nat Genet. 2012 Feb 26;44(4):445-9, S1. doi: 10.1038/ng.1105. PMID:22366787 doi:10.1038/ng.1105

[3] Kitagawa H, Fujiki R, Yoshimura K, Mezaki Y, Uematsu Y, Matsui D, Ogawa S, Unno K, Okubo M, Tokita A, Nakagawa T, Ito T, Ishimi Y, Nagasawa H, Matsumoto T, Yanagisawa J, Kato S. The chromatin-remodeling complex WINAC targets a nuclear receptor to promoters and is impaired in Williams syndrome. Cell. 2003 Jun 27;113(7):905-17. PMID:12837248

[1]

[2]

[3]

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 5dkh is ON HOLD
+==Crystal structure of the bromodomain of human BRM (SMARCA2) in complex with a hydroxyphenyl propenone inhibitor 17==
+<StructureSection load='5dkh' size='340' side='right'caption='[[5dkh]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
-Authors: Tallant, C., Owen, D.R., Taylor, A., Fedorov, O., Savitsky, P., Siejka, P., Srikannathasan, V., Nowak, R., von Delft, F., Arrowsmith, C.H., Edwards, A.M., Bountra, C., Knapp, S.
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5dkh]] 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=5DKH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5DKH FirstGlance]. <br>
-Description: Crystal structure of the bromodomain of human BRM (SMARCA2) in complex with a hydroxyphenyl propenone inhibitor 17
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7&#8491;</td></tr>
-[[Category: Unreleased Structures]]
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5C0:(2E)-3-[(6S,9R)-4-(CYCLOPROPYLAMINO)-6,7,8,9-TETRAHYDRO-5H-6,9-EPIMINOCYCLOHEPTA[D]PYRIMIDIN-10-YL]-1-(2-HYDROXYPHENYL)PROP-2-EN-1-ONE'>5C0</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-[[Category: Nowak, R]]
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5dkh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dkh OCA], [https://pdbe.org/5dkh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5dkh RCSB], [https://www.ebi.ac.uk/pdbsum/5dkh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5dkh ProSAT]</span></td></tr>
-[[Category: Owen, D.R]]
+</table>
-[[Category: Fedorov, O]]
+== Disease ==
-[[Category: Siejka, P]]
+[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>
-[[Category: Knapp, S]]
+== Function ==
-[[Category: Bountra, C]]
+[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>
-[[Category: Arrowsmith, C.H]]
+== References ==
-[[Category: Von Delft, F]]
+<references/>
-[[Category: Taylor, A]]
+__TOC__
-[[Category: Edwards, A.M]]
+</StructureSection>
-[[Category: Tallant, C]]
+[[Category: Homo sapiens]]
-[[Category: Srikannathasan, V]]
+[[Category: Large Structures]]
-[[Category: Savitsky, P]]
+[[Category: Arrowsmith CH]]
+[[Category: Bountra C]]
+[[Category: Edwards AM]]
+[[Category: Fedorov O]]
+[[Category: Knapp S]]
+[[Category: Nowak R]]
+[[Category: Owen DR]]
+[[Category: Savitsky P]]
+[[Category: Siejka P]]
+[[Category: Srikannathasan V]]
+[[Category: Tallant C]]
+[[Category: Taylor A]]
+[[Category: Von Delft F]]

5dkh: Difference between revisions

Latest revision as of 00:46, 29 June 2023

Crystal structure of the bromodomain of human BRM (SMARCA2) in complex with a hydroxyphenyl propenone inhibitor 17Crystal structure of the bromodomain of human BRM (SMARCA2) in complex with a hydroxyphenyl propenone inhibitor 17

Structural highlights

Disease

Function

References

Contents

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5dkh: Difference between revisions

Latest revision as of 00:46, 29 June 2023

Crystal structure of the bromodomain of human BRM (SMARCA2) in complex with a hydroxyphenyl propenone inhibitor 17Crystal structure of the bromodomain of human BRM (SMARCA2) in complex with a hydroxyphenyl propenone inhibitor 17

Structural highlights

Disease

Function

References

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