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Publication Abstract from PubMed

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.

Structural insights into substrate recognition and activity regulation of the key decarboxylase SbnH in staphyloferrin B biosynthesis.,Tang J, Ju Y, Gu Q, Xu J, Zhou H J Mol Biol. 2019 Oct 18. pii: S0022-2836(19)30605-9. doi:, 10.1016/j.jmb.2019.10.009. PMID:31634470^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.