4MEB

Crystal structure of aCif-D158S

Summary for 4MEB

• Entry DOI: 10.2210/pdb4meb/pdb
• Related: 3KD2 4MEA
• Descriptor: Predicted protein, PHOSPHATE ION, GLYCEROL, ... (4 entities in total)
• Functional Keywords: alpha/beta hydrolase fold, epoxide hydrolase, secreted, hydrolase
• Biological source: Acinetobacter sp. RUH2624
• Total number of polymer chains: 2
• Total formula weight: 74036.70

Authors

Bridges, A.A.,Bahl, C.D.,Madden, D.R. (deposition date: 2013-08-25, release date: 2014-02-05, Last modification date: 2023-09-20)

Primary citation

Bahl, C.D.,Hvorecny, K.L.,Bridges, A.A.,Ballok, A.E.,Bomberger, J.M.,Cady, K.C.,O'Toole, G.A.,Madden, D.R.
Signature motifs identify an acinetobacter cif virulence factor with epoxide hydrolase activity.
J.Biol.Chem., 289:7460-7469, 2014

PubMed Abstract: Endocytic recycling of the cystic fibrosis transmembrane conductance regulator (CFTR) is blocked by the CFTR inhibitory factor (Cif). Originally discovered in Pseudomonas aeruginosa, Cif is a secreted epoxide hydrolase that is transcriptionally regulated by CifR, an epoxide-sensitive repressor. In this report, we investigate a homologous protein found in strains of the emerging nosocomial pathogens Acinetobacter nosocomialis and Acinetobacter baumannii ("aCif"). Like Cif, aCif is an epoxide hydrolase that carries an N-terminal secretion signal and can be purified from culture supernatants. When applied directly to polarized airway epithelial cells, mature aCif triggers a reduction in CFTR abundance at the apical membrane. Biochemical and crystallographic studies reveal a dimeric assembly with a stereochemically conserved active site, confirming our motif-based identification of candidate Cif-like pathogenic EH sequences. Furthermore, cif expression is transcriptionally repressed by a CifR homolog ("aCifR") and is induced in the presence of epoxides. Overall, this Acinetobacter protein recapitulates the essential attributes of the Pseudomonas Cif system and thus may facilitate airway colonization in nosocomial lung infections.

PubMed: 24474692
DOI: 10.1074/jbc.M113.518092

Experimental method

X-RAY DIFFRACTION (2 Å)