5G10

Pseudomonas aeruginosa HDAH bound to 9,9,9 trifluoro-8,8-dihydroy-N-phenylnonanamide

Summary for 5G10

• Entry DOI: 10.2210/pdb5g10/pdb
• Related: 5G0X 5G0Y 5G11 5G12 5G13 5G14 5G17
• Descriptor: HDAH, ZINC ION, POTASSIUM ION, ... (5 entities in total)
• Functional Keywords: hydrolase, hdah, hdac, hdlp
• Biological source: PSEUDOMONAS AERUGINOSA
• Total number of polymer chains: 2
• Total formula weight: 82860.33

Authors

Kraemer, A.,Meyer-Almes, F.J.,Yildiz, O. (deposition date: 2016-03-23, release date: 2016-11-30, Last modification date: 2024-01-10)

Primary citation

Kramer, A.,Wagner, T.,Yildiz, O.,Meyer-Almes, F.J.
Crystal Structure of a Histone Deacetylase Homologue from Pseudomonas aeruginosa.
Biochemistry, 55:6858-6868, 2016

PubMed Abstract: 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 PA3774 mutant, the inhibitor-free PA3774 mutant, and the PA3774 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.

PubMed: 27951649
DOI: 10.1021/acs.biochem.6b00613

Experimental method

X-RAY DIFFRACTION (1.71 Å)