5g10: Difference between revisions
New page: '''Unreleased structure''' The entry 5g10 is ON HOLD Authors: Kraemer, A., Meyer-Almes, F.J., Yildiz, O. Description: Pseudomonas aeruginosa HDAH bound to 9,9,9 trifluoro-8,8-dihydroy-... |
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==Pseudomonas aeruginosa HDAH bound to 9,9,9 trifluoro-8,8-dihydroy-N-phenylnonanamide== | |||
<StructureSection load='5g10' size='340' side='right'caption='[[5g10]], [[Resolution|resolution]] 1.71Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5g10]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa_PAO1 Pseudomonas aeruginosa PAO1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5G10 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5G10 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]] 1.71Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6DK:9,9,9-TRIS(FLUORANYL)-8,8-BIS(OXIDANYL)-~{N}-PHENYL-NONANAMIDE'>6DK</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=5g10 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5g10 OCA], [https://pdbe.org/5g10 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5g10 RCSB], [https://www.ebi.ac.uk/pdbsum/5g10 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5g10 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/HDAH_PSEAE HDAH_PSEAE] Probable protein deacetylase that catalyzes deacetylation of acetylated lysine residues. In vitro, exhibits high activity against artificial HDAC (histone deacetylase) substrates containing acetylated and trifluoroacetylated lysine residues. Is not able to deacetylate acetylated polyamines.<ref>PMID:26956223</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Despite the recently growing interest in the acetylation of lysine residues by prokaryotic enzymes, the underlying biological function is still not well understood. Deacetylation is accomplished by proteins that belong to the histone deacetylase (HDAC) superfamily. In this report, we present the first crystal structure of PA3774, a histone deacetylase homologue from the human pathogen Pseudomonas aeruginosa that shares a high degree of homology with class IIb HDACs. We determined the crystal structure of the ligand-free enzyme and protein-ligand complexes with a trifluoromethylketone inhibitor and the reaction product acetate. Moreover, we produced loss of function mutants and determined the structure of the inhibitor-free PA3774H143A mutant, the inhibitor-free PA3774Y313F mutant, and the PA3774Y313F mutant in complex with the highly selective hydroxamate inhibitor PFSAHA. The overall structure reveals that the exceptionally long L1 loop mediates the formation of a tetramer composed of two "head-to-head" dimers. The distinctive dimer interface significantly confines the entrance area of the active site, suggesting a crucial role for substrate recognition and selectivity. | |||
Crystal Structure of a Histone Deacetylase Homologue from Pseudomonas aeruginosa.,Kramer A, Wagner T, Yildiz O, Meyer-Almes FJ Biochemistry. 2016 Dec 13;55(49):6858-6868. Epub 2016 Nov 29. PMID:27951649<ref>PMID:27951649</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 5g10" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
[[Category: Meyer-Almes | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Pseudomonas aeruginosa PAO1]] | |||
[[Category: Kraemer A]] | |||
[[Category: Meyer-Almes FJ]] | |||
[[Category: Yildiz O]] | |||
Latest revision as of 16:34, 26 July 2023
Pseudomonas aeruginosa HDAH bound to 9,9,9 trifluoro-8,8-dihydroy-N-phenylnonanamidePseudomonas aeruginosa HDAH bound to 9,9,9 trifluoro-8,8-dihydroy-N-phenylnonanamide
Structural highlights
FunctionHDAH_PSEAE Probable protein deacetylase that catalyzes deacetylation of acetylated lysine residues. In vitro, exhibits high activity against artificial HDAC (histone deacetylase) substrates containing acetylated and trifluoroacetylated lysine residues. Is not able to deacetylate acetylated polyamines.[1] Publication Abstract from PubMedDespite the recently growing interest in the acetylation of lysine residues by prokaryotic enzymes, the underlying biological function is still not well understood. Deacetylation is accomplished by proteins that belong to the histone deacetylase (HDAC) superfamily. In this report, we present the first crystal structure of PA3774, a histone deacetylase homologue from the human pathogen Pseudomonas aeruginosa that shares a high degree of homology with class IIb HDACs. We determined the crystal structure of the ligand-free enzyme and protein-ligand complexes with a trifluoromethylketone inhibitor and the reaction product acetate. Moreover, we produced loss of function mutants and determined the structure of the inhibitor-free PA3774H143A mutant, the inhibitor-free PA3774Y313F mutant, and the PA3774Y313F mutant in complex with the highly selective hydroxamate inhibitor PFSAHA. The overall structure reveals that the exceptionally long L1 loop mediates the formation of a tetramer composed of two "head-to-head" dimers. The distinctive dimer interface significantly confines the entrance area of the active site, suggesting a crucial role for substrate recognition and selectivity. Crystal Structure of a Histone Deacetylase Homologue from Pseudomonas aeruginosa.,Kramer A, Wagner T, Yildiz O, Meyer-Almes FJ Biochemistry. 2016 Dec 13;55(49):6858-6868. Epub 2016 Nov 29. PMID:27951649[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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