4WHN

Structure of toxin-activating acyltransferase (TAAT)

4WHN の概要

• エントリーDOI: 10.2210/pdb4whn/pdb
• 分子名称: ApxC, CITRIC ACID (3 entities in total)
• 機能のキーワード: taat, gnat, toxin-activating acyltransferase, acp binding, transferase
• 由来する生物種: Actinobacillus pleuropneumoniae
• 細胞内の位置: Cytoplasm : P55132
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 84972.66

構造登録者

Crow, A.,Greene, N.P.,Hughes, C.,Koronakis, V. (登録日: 2014-09-23, 公開日: 2015-06-03, 最終更新日: 2024-05-08)

主引用文献

Greene, N.P.,Crow, A.,Hughes, C.,Koronakis, V.
Structure of a bacterial toxin-activating acyltransferase.
Proc.Natl.Acad.Sci.USA, 112:E3058-E3066, 2015

PubMed Abstract: Secreted pore-forming toxins of pathogenic Gram-negative bacteria such as Escherichia coli hemolysin (HlyA) insert into host-cell membranes to subvert signal transduction and induce apoptosis and cell lysis. Unusually, these toxins are synthesized in an inactive form that requires posttranslational activation in the bacterial cytosol. We have previously shown that the activation mechanism is an acylation event directed by a specialized acyl-transferase that uses acyl carrier protein (ACP) to covalently link fatty acids, via an amide bond, to specific internal lysine residues of the protoxin. We now reveal the 2.15-Å resolution X-ray structure of the 172-aa ApxC, a toxin-activating acyl-transferase (TAAT) from pathogenic Actinobacillus pleuropneumoniae. This determination shows that bacterial TAATs are a structurally homologous family that, despite indiscernible sequence similarity, form a distinct branch of the Gcn5-like N-acetyl transferase (GNAT) superfamily of enzymes that typically use acyl-CoA to modify diverse bacterial, archaeal, and eukaryotic substrates. A combination of structural analysis, small angle X-ray scattering, mutagenesis, and cross-linking defined the solution state of TAATs, with intermonomer interactions mediated by an N-terminal α-helix. Superposition of ApxC with substrate-bound GNATs, and assay of toxin activation and binding of acyl-ACP and protoxin peptide substrates by mutated ApxC variants, indicates the enzyme active site to be a deep surface groove.

PubMed: 26016525
DOI: 10.1073/pnas.1503832112

実験手法

X-RAY DIFFRACTION (2.15 Å)