6fuk: Difference between revisions

Line 1:

~~'''Unreleased structure'''~~

The entry ~~6fuk~~ is ~~ON HOLD~~

==Crystal structure of UTX complexed with 5-carboxy-8-hydroxyquinoline==

== Structural highlights ==

<table><tr><td colspan='2'>[[6fuk]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FUK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FUK FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8XQ:8-HYDROXYQUINOLINE-5-CARBOXYLIC+ACID'>8XQ</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PG0:2-(2-METHOXYETHOXY)ETHANOL'>PG0</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=6fuk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fuk OCA], [http://pdbe.org/6fuk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6fuk RCSB], [http://www.ebi.ac.uk/pdbsum/6fuk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6fuk ProSAT]</span></td></tr>

</table>

== Disease ==

[[http://www.uniprot.org/uniprot/KDM6A_HUMAN KDM6A_HUMAN]] Kabuki syndrome. The disease is caused by mutations affecting the gene represented in this entry.

== Function ==

[[http://www.uniprot.org/uniprot/KDM6A_HUMAN KDM6A_HUMAN]] Histone demethylase that specifically demethylates 'Lys-27' of histone H3, thereby playing a central role in histone code. Demethylates trimethylated and dimethylated but not monomethylated H3 'Lys-27'. Plays a central role in regulation of posterior development, by regulating HOX gene expression. Demethylation of 'Lys-27' of histone H3 is concomitant with methylation of 'Lys-4' of histone H3, and regulates the recruitment of the PRC1 complex and monoubiquitination of histone H2A.<ref>PMID:17851529</ref> <ref>PMID:17761849</ref>

== Publication Abstract from PubMed ==

In the search for new demethylase inhibitors, we have developed a multistep protocol for in silico screening. Millions of poses generated by high-throughput docking or a 3D-pharmacophore search are first minimized by a classical force field and then filtered by semiempirical quantum mechanical calculations of the interaction energy with a selected set of functional groups in the binding site. The final ranking includes solvation effects which are evaluated in the continuum dielectric approximation (finite-difference Poisson equation). Application of the multistep protocol to JMJD3 jumonji demethylase has resulted in a dozen low-micromolar inhibitors belonging to five different chemical classes. We have solved the crystal structure of JMJD3 inhibitor 8 in the complex with UTX (a demethylase in the same subfamily as JMJD3) which validates the predicted binding mode. Compound 8 is a promising candidate for future optimization as it has a favorable ligand efficiency of 0.32 kcal/mol per nonhydrogen atom.

~~Authors:~~ Esposito, C~~., Sledz~~, P., Caflisch, A.

In Silico Identification of JMJD3 Demethylase Inhibitors.,Esposito C, Wiedmer L, Caflisch A J Chem Inf Model. 2018 Oct 3. doi: 10.1021/acs.jcim.8b00539. PMID:30226987<ref>PMID:30226987</ref>

~~Description: Crystal structure~~ of ~~UTX complexed with 5~~-~~carboxy~~-~~8-hydroxyquinoline~~

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

[[Category: ~~Unreleased Structures~~]]

</div>

== References ==

__TOC__

</StructureSection>

[[Category: Caflisch, A]]

[[Category: Esposito, C]]

[[Category: Sledz, P]]

[[Category: ~~Esposito, C~~]]

[[Category: Inhibitor]]

[[Category: ~~Caflisch, A~~]]

[[Category: Jumonji demethylase]]

[[Category: Oxidoreductase]]

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@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 6fuk is ON HOLD
+==Crystal structure of UTX complexed with 5-carboxy-8-hydroxyquinoline==
+<StructureSection load='6fuk' size='340' side='right' caption='[[6fuk]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6fuk]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FUK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FUK FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8XQ:8-HYDROXYQUINOLINE-5-CARBOXYLIC+ACID'>8XQ</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PG0:2-(2-METHOXYETHOXY)ETHANOL'>PG0</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=6fuk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fuk OCA], [http://pdbe.org/6fuk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6fuk RCSB], [http://www.ebi.ac.uk/pdbsum/6fuk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6fuk ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[[http://www.uniprot.org/uniprot/KDM6A_HUMAN KDM6A_HUMAN]] Kabuki syndrome. The disease is caused by mutations affecting the gene represented in this entry.
+== Function ==
+[[http://www.uniprot.org/uniprot/KDM6A_HUMAN KDM6A_HUMAN]] Histone demethylase that specifically demethylates 'Lys-27' of histone H3, thereby playing a central role in histone code. Demethylates trimethylated and dimethylated but not monomethylated H3 'Lys-27'. Plays a central role in regulation of posterior development, by regulating HOX gene expression. Demethylation of 'Lys-27' of histone H3 is concomitant with methylation of 'Lys-4' of histone H3, and regulates the recruitment of the PRC1 complex and monoubiquitination of histone H2A.<ref>PMID:17851529</ref> <ref>PMID:17761849</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+In the search for new demethylase inhibitors, we have developed a multistep protocol for in silico screening. Millions of poses generated by high-throughput docking or a 3D-pharmacophore search are first minimized by a classical force field and then filtered by semiempirical quantum mechanical calculations of the interaction energy with a selected set of functional groups in the binding site. The final ranking includes solvation effects which are evaluated in the continuum dielectric approximation (finite-difference Poisson equation). Application of the multistep protocol to JMJD3 jumonji demethylase has resulted in a dozen low-micromolar inhibitors belonging to five different chemical classes. We have solved the crystal structure of JMJD3 inhibitor 8 in the complex with UTX (a demethylase in the same subfamily as JMJD3) which validates the predicted binding mode. Compound 8 is a promising candidate for future optimization as it has a favorable ligand efficiency of 0.32 kcal/mol per nonhydrogen atom.
-Authors: Esposito, C., Sledz, P., Caflisch, A.
+In Silico Identification of JMJD3 Demethylase Inhibitors.,Esposito C, Wiedmer L, Caflisch A J Chem Inf Model. 2018 Oct 3. doi: 10.1021/acs.jcim.8b00539. PMID:30226987<ref>PMID:30226987</ref>
-Description: Crystal structure of UTX complexed with 5-carboxy-8-hydroxyquinoline
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 6fuk" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Caflisch, A]]
+[[Category: Esposito, C]]
 [[Category: Sledz, P]]
-[[Category: Esposito, C]]
+[[Category: Inhibitor]]
-[[Category: Caflisch, A]]
+[[Category: Jumonji demethylase]]
+[[Category: Oxidoreductase]]