6KNH

Crystal structure of SbnH in complex with citrate, a PLP-dependent decarboxylase in Staphyloferrin B biothesynthesis

Summary for 6KNH

• Entry DOI: 10.2210/pdb6knh/pdb
• Descriptor: Probable diaminopimelate decarboxylase protein, CITRIC ACID, PHOSPHATE ION, ... (4 entities in total)
• Functional Keywords: plp-dependent decarboxylase, staphyloferrin b, biosynthetic protein
• Biological source: Staphylococcus aureus subsp. aureus Mu50
• Total number of polymer chains: 3
• Total formula weight: 140644.53

Authors

Tang, J.,Ju, Y.,Zhou, H. (deposition date: 2019-08-05, release date: 2019-11-13, Last modification date: 2023-11-22)

Primary citation

Tang, J.,Ju, Y.,Gu, Q.,Xu, J.,Zhou, H.
Structural Insights into Substrate Recognition and Activity Regulation of the Key Decarboxylase SbnH in Staphyloferrin B Biosynthesis.
J.Mol.Biol., 431:4868-4881, 2019

PubMed 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 freestanding 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.

PubMed: 31634470
DOI: 10.1016/j.jmb.2019.10.009

Experimental method

X-RAY DIFFRACTION (1.76 Å)