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5t4u

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Revision as of 11:21, 16 September 2020

Crystal structure of the bromodomain of human BRPF1 in complex with a quinolinone ligand

Structural highlights

5t4u is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Gene:	BRPF1, BR140 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[BRPF1_HUMAN] Component of the MOZ/MORF complex which has a histone H3 acetyltransferase activity. Positively regulates the transcription of RUNX1 and RUNX2.^[1] ^[2]

Publication Abstract from PubMed

The BRPF (bromodomain and PHD finger-containing) family are scaffolding proteins important for the recruitment of histone acetyltransferases of the MYST family to chromatin. Evaluation of the BRPF family as a potential drug target is at an early stage although there is an emerging understanding of a role in acute myeloid leukemia (AML). We report the optimization of fragment hit 5b to 13-d as a biased, potent inhibitor of the BRD of the BRPFs with excellent selectivity over nonclass IV BRD proteins. Evaluation of 13-d in a panel of cancer cell lines showed a selective inhibition of proliferation of a subset of AML lines. Pharmacokinetic studies established that 13-d had properties compatible with oral dosing in mouse models of disease (Fpo 49%). We propose that NI-42 (13-d) is a new chemical probe for the BRPFs suitable for cellular and in vivo studies to explore the fundamental biology of these proteins.

Design of a Biased Potent Small Molecule Inhibitor of the Bromodomain and PHD Finger-Containing (BRPF) Proteins Suitable for Cellular and in Vivo Studies.,Igoe N, Bayle ED, Fedorov O, Tallant C, Savitsky P, Rogers C, Owen DR, Deb G, Somervaille TC, Andrews DM, Jones N, Cheasty A, Ryder H, Brennan PE, Muller S, Knapp S, Fish PV J Med Chem. 2017 Jan 26;60(2):668-680. doi: 10.1021/acs.jmedchem.6b01583. Epub, 2017 Jan 9. PMID:28068087^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Doyon Y, Cayrou C, Ullah M, Landry AJ, Cote V, Selleck W, Lane WS, Tan S, Yang XJ, Cote J. ING tumor suppressor proteins are critical regulators of chromatin acetylation required for genome expression and perpetuation. Mol Cell. 2006 Jan 6;21(1):51-64. PMID:16387653 doi:10.1016/j.molcel.2005.12.007
↑ Ullah M, Pelletier N, Xiao L, Zhao SP, Wang K, Degerny C, Tahmasebi S, Cayrou C, Doyon Y, Goh SL, Champagne N, Cote J, Yang XJ. Molecular architecture of quartet MOZ/MORF histone acetyltransferase complexes. Mol Cell Biol. 2008 Nov;28(22):6828-43. doi: 10.1128/MCB.01297-08. Epub 2008 Sep , 15. PMID:18794358 doi:10.1128/MCB.01297-08
↑ Igoe N, Bayle ED, Fedorov O, Tallant C, Savitsky P, Rogers C, Owen DR, Deb G, Somervaille TC, Andrews DM, Jones N, Cheasty A, Ryder H, Brennan PE, Muller S, Knapp S, Fish PV. Design of a Biased Potent Small Molecule Inhibitor of the Bromodomain and PHD Finger-Containing (BRPF) Proteins Suitable for Cellular and in Vivo Studies. J Med Chem. 2017 Jan 26;60(2):668-680. doi: 10.1021/acs.jmedchem.6b01583. Epub, 2017 Jan 9. PMID:28068087 doi:http://dx.doi.org/10.1021/acs.jmedchem.6b01583

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5t4u"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the bromodomain of human BRPF1 in complex with a quinolinone ligand==
-<StructureSection load='5t4u' size='340' side='right' caption='[[5t4u]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
+<StructureSection load='5t4u' size='340' side='right'caption='[[5t4u]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5t4u]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5T4U OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5T4U FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5t4u]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5T4U OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5T4U FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=12Q:1-METHYLQUINOLIN-2(1H)-ONE'>12Q</scene>, <scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=12Q:1-METHYLQUINOLIN-2(1H)-ONE'>12Q</scene>, <scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene></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=5t4u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5t4u OCA], [http://pdbe.org/5t4u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5t4u RCSB], [http://www.ebi.ac.uk/pdbsum/5t4u PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5t4u ProSAT]</span></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BRPF1, BR140 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5t4u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5t4u OCA], [http://pdbe.org/5t4u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5t4u RCSB], [http://www.ebi.ac.uk/pdbsum/5t4u PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5t4u ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 18: / Line 19: @@
 </div>
 <div class="pdbe-citations 5t4u" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Peregrin|Peregrin]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Arrowsmith, C H]]
 [[Category: Bayle, E D]]

5t4u

From Proteopedia

Revision as of 11:21, 16 September 2020

Crystal structure of the bromodomain of human BRPF1 in complex with a quinolinone ligand

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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