5g0x
Pseudomonas aeruginosa HDAH bound to acetate.Pseudomonas aeruginosa HDAH bound to acetate.
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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