Pseudomonas aeruginosa is a Gram-negative bacterium that is a major cause of potentially life-threatening healthcare-associated infections. The bacteria typically infect immune-compromised patients with severe burns, wounds, AIDS, or cystic fibrosis, and. cause generalized inflammation and sepsis. P. aeruginosa also exhibits an extraordinary ability to acquire resistance to antibiotics.
Researchers from the NIAID Center for Structural Genomics of Infectious Diseases, in collaboration with the Midwest Center for Structural Genomics, have developed and used semi-high-throughput crystallographic and biochemical screening approaches to structurally and functionally characterize a previously uncharacterized protein from P. aeruginosa, PA4794.
The researchers confirmed that PA4794 has N-acetyltransferase activity, and selectively acetylates peptides with a C-terminal lysine at the Nε atom. Lysine acetylation is a protein modification with great regulatory potential. PA4794 could prove to be a drug discovery target, as it is involved in many aspects of cellular physiology.
Researchers obtained the structure of the ternary complex of PA4794 with its reaction products, CoA and acetylated peptide. Moreover, they have shown that several cephalosporin antibiotics competitively inhibit peptide acetylation. Understanding PA4794-antibiotic interactions may be useful in facilitating the design of more optimal inhibitors.
Structure of PA4794 (grey) in complex with the products of the reaction: acetylated peptide (green) and CoA (blue). For more information see Protein Data Bank structures 4KUA, 3PGP, 4KUB, 4L89, 4L8A, 4KLV, 4KOT, 4KOW, 4KOX, 4KOV, 4KOU, 4KOY, 4KOR, 4KOS, and 4KLW.
Structural, functional, and inhibition studies of a Gcn5-related N-acetyltransferase (GNAT) superfamily protein PA4794: a new C-terminal lysine protein acetyltransferase from Pseudomonas aeruginosa. Majorek KA, Kuhn ML, Chruszcz M, Anderson WF, Minor W. J Biol Chem. 2013 Oct 18;288(42):30223-35. doi: 10.1074/jbc.M113.501353.
All featured structures from the NIAID Structural Genomics Centers
Last Updated January 06, 2014