5mwz: Difference between revisions

Revision as of 06:40, 16 October 2019

Crystal structure of the human BRPF1 bromodomain in complex with BZ073

Structural highlights

5mwz 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:	KGU
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

Bromodomain and plant homeodomain (PHD) finger containing protein 1 (BRPF1) is a member of subfamily IV of the human bromodomains. Experimental evidence suggests that BRPF1 is involved in leukemia. In a previous high-throughput docking campaign we identified several chemotypes targeting the BRPF1 bromodomain. Here, pharmacophore searches using the binding modes of two of these chemotypes resulted in two new series of ligands of the BRPF1 bromodomain. The 2,3-dioxo-quinoxaline 21 exhibits a 2-muM affinity for the BRPF1 bromodomain in two different competition binding assays, and more than 100-fold selectivity for BRPF1 against other members of subfamily IV and representatives of other subfamilies. Cellular activity is confirmed by a viability assay in a leukemia cell line. Isothermal titration calorimetry measurements reveal enthalpy-driven binding for compounds 21, 26 (KD=3muM), and the 2,4-dimethyl-oxazole derivative 42 (KD=10muM). Multiple molecular dynamics simulations and a dozen co-crystal structures at high resolution provide useful information for further optimization of affinity for the BRPF1 bromodomain.

Structure-based discovery of selective BRPF1 bromodomain inhibitors.,Zhu J, Zhou C, Caflisch A Eur J Med Chem. 2018 Jun 2;155:337-352. doi: 10.1016/j.ejmech.2018.05.037. PMID:29902720^[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
↑ Zhu J, Zhou C, Caflisch A. Structure-based discovery of selective BRPF1 bromodomain inhibitors. Eur J Med Chem. 2018 Jun 2;155:337-352. doi: 10.1016/j.ejmech.2018.05.037. PMID:29902720 doi:https://dx.doi.org/10.1016/j.ejmech.2018.05.037

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] 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

[2] 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

[3] Zhu J, Zhou C, Caflisch A. Structure-based discovery of selective BRPF1 bromodomain inhibitors. Eur J Med Chem. 2018 Jun 2;155:337-352. doi: 10.1016/j.ejmech.2018.05.037. PMID:29902720 doi:https://dx.doi.org/10.1016/j.ejmech.2018.05.037

[1]

[2]

[3]

@@ Line 1: / Line 1: @@
 ==Crystal structure of the human BRPF1 bromodomain in complex with BZ073==
-<StructureSection load='5mwz' size='340' side='right' caption='[[5mwz]], [[Resolution|resolution]] 1.25&Aring;' scene=''>
+<StructureSection load='5mwz' size='340' side='right'caption='[[5mwz]], [[Resolution|resolution]] 1.25&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[5mwz]] 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=5MWZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5MWZ FirstGlance]. <br>
@@ Line 19: / Line 19: @@
 </div>
 <div class="pdbe-citations 5mwz" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Peregrin|Peregrin]]
 == References ==
 <references/>
@@ Line 24: / Line 27: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Caflisch, A]]
 [[Category: Zhu, J]]

5mwz: Difference between revisions

Revision as of 06:40, 16 October 2019

Crystal structure of the human BRPF1 bromodomain in complex with BZ073

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Navigation menu

Page actions

Page actions

Personal tools

Navigation

Search

Tools