Structural insights into substrate recognition and activity regulation of the key decarboxylase SbnH in staphyloferrin B biosynthesis

Publication date: Available online 18 October 2019Source: Journal of Molecular BiologyAuthor(s): Jieyu Tang, Yingchen Ju, Qiong Gu, Jun Xu, Huihao ZhouAbstractStaphyloferrin 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 ...
Source: Journal of Molecular Biology - Category: Molecular Biology Source Type: research