6xvc: Difference between revisions
New page: '''Unreleased structure''' The entry 6xvc is ON HOLD Authors: Description: Category: Unreleased Structures |
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==CRYSTAL STRUCTURE OF BRD4-BD1 WITH COMPOUND 1== | |||
<StructureSection load='6xvc' size='340' side='right'caption='[[6xvc]], [[Resolution|resolution]] 1.10Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6xvc]] 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=6XVC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6XVC 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]] 1.098Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=O32:(4~{R})-4-[(1~{R})-1-[7-(3-methyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl)quinolin-5-yl]oxyethyl]pyrrolidin-2-one'>O32</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=6xvc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xvc OCA], [https://pdbe.org/6xvc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6xvc RCSB], [https://www.ebi.ac.uk/pdbsum/6xvc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6xvc 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> | |||
== Function == | |||
[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 == | |||
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<ref>PMID:32421895</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6xvc" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Bader G]] | |||
[[Category: Kessler D]] | |||
[[Category: Wolkerstorfer B]] | |||
Latest revision as of 16:13, 24 January 2024
CRYSTAL STRUCTURE OF BRD4-BD1 WITH COMPOUND 1CRYSTAL STRUCTURE OF BRD4-BD1 WITH COMPOUND 1
Structural highlights
DiseaseBRD4_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] FunctionBRD4_HUMAN Plays a role in a process governing chromosomal dynamics during mitosis (By similarity). Publication Abstract from PubMedWhile 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
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