|
type |
Journal Article |
authors |
Tang J, Ju Y, Gu Q, Xu J, Zhou H |
title |
Structural insights into substrate recognition and activity regulation of the key decarboxylase SbnH in staphyloferrin B biosynthesis |
journal |
J Mol Biol |
Activity |
4.1.1.117 |
Family |
4.1.1.117 |
sel |
selected |
ui |
31634470 |
year |
(2019) |
volume |
431 |
number |
24 |
pages |
4868-4881 |
| |
keywords |
PLP-dependent decarboxylase; Staphylococcus aureus; citrate; crystal structure; endogenous inhibitor |
abstract |
Staphyloferrin B is a hydroxycarboxylate siderophore that is crucial for the invasion and virulence of Staphylococcus aureus in mammalian hosts where free iron ions are scarce. The assembly of staphyloferrin B involves four enzymatic steps, in which SbnH, a pyridoxal 5'-phosphate (PLP)-dependent decarboxylase, catalyzes the second step. Here, we report the X-ray crystal structures of S. aureus SbnH (SaSbnH) in complex with PLP, citrate and the decarboxylation product citryl-diaminoethane (citryl-Dae). The overall structure of SaSbnH resembles those of the previously reported PLP-dependent amino acid decarboxylases, but the active site of SaSbnH showed unique structural features. Structural and mutagenesis analysis revealed that the citryl moiety of the substrate citryl-L-2,3-diaminopropionic acid (citryl-L-Dap) inserts into a narrow groove at the dimer interface of SaSbnH and forms hydrogen bonding interactions with both subunits. In the active site, a conserved lysine residue forms an aldimine linkage with the cofactor PLP, and a phenylalanine residue is essential for accommodating the L-configuration Dap of the substrate. Interestingly, the free-standing citrate molecule was found to bind to SaSbnH in a conformation inverse to that of the citryl group of citryl-Dae and efficiently inhibit SaSbnH. As an intermediate in the tricarboxylic acid (TCA) cycle, citrate is highly abundant in bacterial cells until iron depletion; thus, its inhibition of SaSbnH may serve as an iron-dependent regulatory mechanism in staphyloferrin B biosynthesis. |
last changed |
2020/02/17 09:38 |
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