6xuz

From Proteopedia

(Difference between revisions)

Current revision

CRYSTAL STRUCTURE OF BRD4-BD1 WITH COMPOUND 4

Structural highlights

6xuz is a 1 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 1.07Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

BRD4_HUMAN Note=A chromosomal aberration involving BRD4 is found in a rare, aggressive, and lethal carcinoma arising in midline organs of young people. Translocation t(15;19)(q14;p13) with NUT which produces a BRD4-NUT fusion protein.^[1] ^[2]

Function

BRD4_HUMAN Plays a role in a process governing chromosomal dynamics during mitosis (By similarity).

Publication Abstract from PubMed

While CH-pi-interactions with target proteins are crucial determinants for the affinity of arguably every drug molecule, no method exists to directly measure the strength of individual CH-pi interactions in drug-protein complexes. Here we present a fast and reliable methodology called PI (pi interactions) by NMR, which can differentiate the strength of protein-ligand CH-pi interactions in solution. By combining selective amino-acid side-chain labeling with 1 H- 13 C NMR, we are able to identify specific protein protons of side-chains engaged in CH-pi interactions with aromatic ring-systems of a ligand, based solely on 1 H chemical shift values of the interacting protein aromatic ring protons. The information encoded in the chemical shifts induced by such interactions serves as a proxy for the strength of each individual CH-pi interaction. PI by NMR changes the paradigm by which chemists can optimize the potency of drug candidates: direct determination of individual pi-interactions rather than averaged measures of all interactions.

PI by NMR: Probing CH-pi Interactions in Protein-Ligand Complexes by NMR.,Platzer G, Mayer M, Beier A, Bruschweiler S, Fuchs JE, Engelhardt H, Geist L, Bader G, Schorghuber J, Lichtenecker R, Wolkersdorfer B, Kessler D, McConnell DB, Konrat R Angew Chem Int Ed Engl. 2020 May 18. doi: 10.1002/anie.202003732. PMID:32421895^[3]

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

References

↑ French CA, Miyoshi I, Kubonishi I, Grier HE, Perez-Atayde AR, Fletcher JA. BRD4-NUT fusion oncogene: a novel mechanism in aggressive carcinoma. Cancer Res. 2003 Jan 15;63(2):304-7. PMID:12543779
↑ French CA, Miyoshi I, Aster JC, Kubonishi I, Kroll TG, Dal Cin P, Vargas SO, Perez-Atayde AR, Fletcher JA. BRD4 bromodomain gene rearrangement in aggressive carcinoma with translocation t(15;19). Am J Pathol. 2001 Dec;159(6):1987-92. PMID:11733348 doi:10.1016/S0002-9440(10)63049-0
↑ Platzer G, Mayer M, Beier A, Bruschweiler S, Fuchs JE, Engelhardt H, Geist L, Bader G, Schorghuber J, Lichtenecker R, Wolkersdorfer B, Kessler D, McConnell DB, Konrat R. PI by NMR: Probing CH-pi Interactions in Protein-Ligand Complexes by NMR. Angew Chem Int Ed Engl. 2020 May 18. doi: 10.1002/anie.202003732. PMID:32421895 doi:http://dx.doi.org/10.1002/anie.202003732

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6xuz"

Categories: Homo sapiens | Large Structures | Bader G | Kessler D | Wolkerstorfer B

@@ Line 3: / Line 3: @@
 <StructureSection load='6xuz' size='340' side='right'caption='[[6xuz]], [[Resolution|resolution]] 1.07&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6xuz]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6XUZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6XUZ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6xuz]] is a 1 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=6XUZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6XUZ FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=O1W:6-[1-[(2~{S})-1-methoxypropan-2-yl]-6-[(3~{S})-3-methylmorpholin-4-yl]imidazo[4,5-c]pyridin-2-yl]-3-methyl-~{N}-propan-2-yl-[1,2,4]triazolo[4,3-a]pyrazin-8-amine'>O1W</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.07&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BRD4, HUNK1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=O1W:6-[1-[(2~{S})-1-methoxypropan-2-yl]-6-[(3~{S})-3-methylmorpholin-4-yl]imidazo[4,5-c]pyridin-2-yl]-3-methyl-~{N}-propan-2-yl-[1,2,4]triazolo[4,3-a]pyrazin-8-amine'>O1W</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=6xuz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xuz OCA], [https://pdbe.org/6xuz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6xuz RCSB], [https://www.ebi.ac.uk/pdbsum/6xuz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6xuz ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[https://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN]] Note=A chromosomal aberration involving BRD4 is found in a rare, aggressive, and lethal carcinoma arising in midline organs of young people. Translocation t(15;19)(q14;p13) with NUT which produces a BRD4-NUT fusion protein.<ref>PMID:12543779</ref> <ref>PMID:11733348</ref>
+[https://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN] Note=A chromosomal aberration involving BRD4 is found in a rare, aggressive, and lethal carcinoma arising in midline organs of young people. Translocation t(15;19)(q14;p13) with NUT which produces a BRD4-NUT fusion protein.<ref>PMID:12543779</ref> <ref>PMID:11733348</ref>
 == Function ==
-[[https://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN]] Plays a role in a process governing chromosomal dynamics during mitosis (By similarity).
+[https://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN] Plays a role in a process governing chromosomal dynamics during mitosis (By similarity).
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 25: / Line 25: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Bader, G]]
+[[Category: Bader G]]
-[[Category: Kessler, D]]
+[[Category: Kessler D]]
-[[Category: Wolkerstorfer, B]]
+[[Category: Wolkerstorfer B]]
-[[Category: Bromodomain]]
-[[Category: Complex]]
-[[Category: Inhibitor]]
-[[Category: Transcription]]

6xuz

From Proteopedia

Current revision

CRYSTAL STRUCTURE OF BRD4-BD1 WITH COMPOUND 4

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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