6hpx

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of ENL (MLLT1) in complex with compound 19

Structural highlights

6hpx 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 2.3Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

ENL_HUMAN A chromosomal aberration involving MLLT1 is associated with acute leukemias. Translocation t(11;19)(q23;p13.3) with KMT2A/MLL1. The result is a rogue activator protein.

Function

ENL_HUMAN Component of the super elongation complex (SEC), a complex required to increase the catalytic rate of RNA polymerase II transcription by suppressing transient pausing by the polymerase at multiple sites along the DNA.^[1] ^[2]

Publication Abstract from PubMed

Lysine acetylation is an epigenetic mark that is principally recognized by bromodomains, and recently structurally diverse YEATS domains also emerged as readers of lysine acetyl/acylations. Here we present a crystallography-based strategy and the discovery of fragments binding to the ENL YEATS domain, a potential drug target. Crystal structures combined with synthetic efforts led to the identification of a submicromolar binder, providing first starting points for the development of chemical probes for this reader domain family.

Structure-Based Approach toward Identification of Inhibitory Fragments for Eleven-Nineteen-Leukemia Protein (ENL).,Heidenreich D, Moustakim M, Schmidt J, Merk D, Brennan PE, Fedorov O, Chaikuad A, Knapp S J Med Chem. 2018 Nov 26. doi: 10.1021/acs.jmedchem.8b01457. PMID:30407816^[3]

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

References

↑ Lin C, Smith ER, Takahashi H, Lai KC, Martin-Brown S, Florens L, Washburn MP, Conaway JW, Conaway RC, Shilatifard A. AFF4, a component of the ELL/P-TEFb elongation complex and a shared subunit of MLL chimeras, can link transcription elongation to leukemia. Mol Cell. 2010 Feb 12;37(3):429-37. doi: 10.1016/j.molcel.2010.01.026. PMID:20159561 doi:10.1016/j.molcel.2010.01.026
↑ He N, Liu M, Hsu J, Xue Y, Chou S, Burlingame A, Krogan NJ, Alber T, Zhou Q. HIV-1 Tat and host AFF4 recruit two transcription elongation factors into a bifunctional complex for coordinated activation of HIV-1 transcription. Mol Cell. 2010 May 14;38(3):428-38. doi: 10.1016/j.molcel.2010.04.013. PMID:20471948 doi:10.1016/j.molcel.2010.04.013
↑ Heidenreich D, Moustakim M, Schmidt J, Merk D, Brennan PE, Fedorov O, Chaikuad A, Knapp S. Structure-Based Approach toward Identification of Inhibitory Fragments for Eleven-Nineteen-Leukemia Protein (ENL). J Med Chem. 2018 Nov 26. doi: 10.1021/acs.jmedchem.8b01457. PMID:30407816 doi:http://dx.doi.org/10.1021/acs.jmedchem.8b01457

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/6hpx"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 6hpx is ON HOLD
+==Crystal structure of ENL (MLLT1) in complex with compound 19==
+<StructureSection load='6hpx' size='340' side='right'caption='[[6hpx]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6hpx]] 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=6HPX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6HPX 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]] 2.3&#8491;</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=GKQ:~{N}-[(3-chlorophenyl)methyl]-1-(2-pyrrolidin-1-ylethyl)benzimidazole-5-carboxamide'>GKQ</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=6hpx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hpx OCA], [https://pdbe.org/6hpx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6hpx RCSB], [https://www.ebi.ac.uk/pdbsum/6hpx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6hpx ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/ENL_HUMAN ENL_HUMAN] A chromosomal aberration involving MLLT1 is associated with acute leukemias. Translocation t(11;19)(q23;p13.3) with KMT2A/MLL1. The result is a rogue activator protein.
+== Function ==
+[https://www.uniprot.org/uniprot/ENL_HUMAN ENL_HUMAN] Component of the super elongation complex (SEC), a complex required to increase the catalytic rate of RNA polymerase II transcription by suppressing transient pausing by the polymerase at multiple sites along the DNA.<ref>PMID:20159561</ref> <ref>PMID:20471948</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Lysine acetylation is an epigenetic mark that is principally recognized by bromodomains, and recently structurally diverse YEATS domains also emerged as readers of lysine acetyl/acylations. Here we present a crystallography-based strategy and the discovery of fragments binding to the ENL YEATS domain, a potential drug target. Crystal structures combined with synthetic efforts led to the identification of a submicromolar binder, providing first starting points for the development of chemical probes for this reader domain family.
-Authors: Heidenreich, D., Chaikuad, A., Arrowsmith, C.H., Edwards, A.M., Bountra, C., Knapp, S., Structural Genomics Consortium (SGC)
+Structure-Based Approach toward Identification of Inhibitory Fragments for Eleven-Nineteen-Leukemia Protein (ENL).,Heidenreich D, Moustakim M, Schmidt J, Merk D, Brennan PE, Fedorov O, Chaikuad A, Knapp S J Med Chem. 2018 Nov 26. doi: 10.1021/acs.jmedchem.8b01457. PMID:30407816<ref>PMID:30407816</ref>
-Description: Crystal structure of ENL (MLLT1) in complex with compound 19
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Chaikuad, A]]
+<div class="pdbe-citations 6hpx" style="background-color:#fffaf0;"></div>
-[[Category: Heidenreich, D]]
+== References ==
-[[Category: Knapp, S]]
+<references/>
-[[Category: Edwards, A.M]]
+__TOC__
-[[Category: Arrowsmith, C.H]]
+</StructureSection>
-[[Category: Structural Genomics Consortium (Sgc)]]
+[[Category: Homo sapiens]]
-[[Category: Bountra, C]]
+[[Category: Large Structures]]
+[[Category: Arrowsmith CH]]
+[[Category: Bountra C]]
+[[Category: Chaikuad A]]
+[[Category: Edwards AM]]
+[[Category: Heidenreich D]]
+[[Category: Knapp S]]

6hpx

From Proteopedia

Current revision

Crystal structure of ENL (MLLT1) in complex with compound 19

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox