2gh6: Difference between revisions
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< | ==Crystal structure of a HDAC-like protein with 9,9,9-trifluoro-8-oxo-N-phenylnonan amide bound== | ||
<StructureSection load='2gh6' size='340' side='right'caption='[[2gh6]], [[Resolution|resolution]] 2.20Å' scene=''> | |||
You may | == Structural highlights == | ||
or the | <table><tr><td colspan='2'>[[2gh6]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Alcaligenaceae_bacterium_FB188 Alcaligenaceae bacterium FB188]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GH6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2GH6 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]] 2.203Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CF3:9,9,9-TRIFLUORO-8-OXO-N-PHENYLNONANAMIDE'>CF3</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</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'>[https://proteopedia.org/fgij/fg.htm?mol=2gh6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gh6 OCA], [https://pdbe.org/2gh6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2gh6 RCSB], [https://www.ebi.ac.uk/pdbsum/2gh6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2gh6 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/HDAH_ALCSD HDAH_ALCSD] | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gh/2gh6_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2gh6 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Histone deacetylases (HDACs) have emerged as attractive targets in anticancer drug development. To date, a number of HDAC inhibitors have been developed and most of them are hydroxamic acid derivatives, typified by suberoylanilide hydroxamic acid (SAHA). Not surprisingly, structural information that can greatly enhance the design of novel HDAC inhibitors is so far only available for hydroxamic acids in complex with HDAC or HDAC-like enzymes. Here, the first structure of an enzyme complex with a nonhydroxamate HDAC inhibitor is presented. The structure of the trifluoromethyl ketone inhibitor 9,9,9-trifluoro-8-oxo-N-phenylnonanamide in complex with bacterial FB188 HDAH (histone deacetylase-like amidohydrolase from Bordetella/Alcaligenes strain FB188) has been determined. HDAH reveals high sequential and functional homology to human class 2 HDACs and a high structural homology to human class 1 HDACs. Comparison with the structure of HDAH in complex with SAHA reveals that the two inhibitors superimpose well. However, significant differences in binding to the active site of HDAH were observed. In the presented structure the O atom of the trifluoromethyl ketone moiety is within binding distance of the Zn atom of the enzyme and the F atoms participate in interactions with the enzyme, thereby involving more amino acids in enzyme-inhibitor binding. | |||
Complex structure of a bacterial class 2 histone deacetylase homologue with a trifluoromethylketone inhibitor.,Nielsen TK, Hildmann C, Riester D, Wegener D, Schwienhorst A, Ficner R Acta Crystallogr Sect F Struct Biol Cryst Commun. 2007 Apr 1;63(Pt, 4):270-3. Epub 2007 Mar 23. PMID:17401192<ref>PMID:17401192</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2gh6" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Histone deacetylase 3D structures|Histone deacetylase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | [[Category: Alcaligenaceae bacterium FB188]] | ||
[[Category: Large Structures]] | |||
[[Category: Ficner R]] | |||
== | [[Category: Hildmann C]] | ||
< | [[Category: Nielsen TK]] | ||
[[Category: Alcaligenaceae bacterium | [[Category: Riester D]] | ||
[[Category: Ficner | [[Category: Schwienhorst A]] | ||
[[Category: Hildmann | [[Category: Wegener D]] | ||
[[Category: Nielsen | |||
[[Category: Riester | |||
[[Category: Schwienhorst | |||
[[Category: Wegener | |||
Latest revision as of 12:40, 30 August 2023
Crystal structure of a HDAC-like protein with 9,9,9-trifluoro-8-oxo-N-phenylnonan amide boundCrystal structure of a HDAC-like protein with 9,9,9-trifluoro-8-oxo-N-phenylnonan amide bound
Structural highlights
FunctionEvolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedHistone deacetylases (HDACs) have emerged as attractive targets in anticancer drug development. To date, a number of HDAC inhibitors have been developed and most of them are hydroxamic acid derivatives, typified by suberoylanilide hydroxamic acid (SAHA). Not surprisingly, structural information that can greatly enhance the design of novel HDAC inhibitors is so far only available for hydroxamic acids in complex with HDAC or HDAC-like enzymes. Here, the first structure of an enzyme complex with a nonhydroxamate HDAC inhibitor is presented. The structure of the trifluoromethyl ketone inhibitor 9,9,9-trifluoro-8-oxo-N-phenylnonanamide in complex with bacterial FB188 HDAH (histone deacetylase-like amidohydrolase from Bordetella/Alcaligenes strain FB188) has been determined. HDAH reveals high sequential and functional homology to human class 2 HDACs and a high structural homology to human class 1 HDACs. Comparison with the structure of HDAH in complex with SAHA reveals that the two inhibitors superimpose well. However, significant differences in binding to the active site of HDAH were observed. In the presented structure the O atom of the trifluoromethyl ketone moiety is within binding distance of the Zn atom of the enzyme and the F atoms participate in interactions with the enzyme, thereby involving more amino acids in enzyme-inhibitor binding. Complex structure of a bacterial class 2 histone deacetylase homologue with a trifluoromethylketone inhibitor.,Nielsen TK, Hildmann C, Riester D, Wegener D, Schwienhorst A, Ficner R Acta Crystallogr Sect F Struct Biol Cryst Commun. 2007 Apr 1;63(Pt, 4):270-3. Epub 2007 Mar 23. PMID:17401192[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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