5d84 | pdb_00005d84

Staphyloferrin B precursor biosynthetic enzyme SbnA bound to PLP

spinqualitylabelsall models 5d84, resolution 1.45Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5d84 is a 1 chain structure with sequence from Staae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: MG, PLP Related: 5d85, 5d86, 5d87 Gene: sbnA, NWMN_0060 (STAAE) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [SBNA_STAAE] Probable pyridoxal phosphate-dependent enzyme involved in siderophore biosynthesis. Publication Abstract from PubMed Staphylococcus aureus assembles the siderophore, staphyloferrin B, from L-2,3-diaminopropionic acid (L-Dap), alpha-ketoglutarate and citrate. Recently, SbnA and SbnB were shown to produce L-Dap and alpha-ketoglutarate from O-phospho-L-serine (OPS) and L-glutamate. SbnA is a pyridoxal 5'-phosphate-dependent enzyme with homology to O-acetyl-L-serine sulfhydrylases; however, SbnA utilizes OPS instead of O-acetyl-L-serine (OAS) and L-glutamate serves as a nitrogen donor instead of a sulfide. In this work, we examined how SbnA dictates substrate specificity for OPS and L-glutamate using a combination of X-ray crystallography, enzyme kinetics and site-directed mutagenesis. Analysis of SbnA crystals incubated with OPS revealed the structure of the PLP-alpha-aminoacrylate intermediate. Intermediate formation induced closure of the active site pocket by trapping a bound citrate molecule adjacent to the PLP-alpha-aminoacrylate. The citrate is likely replaced by the substrate L-glutamate during catalysis. Three active site residues were identified: Arg132, Tyr152, Ser185 that were essential for OPS recognition and turnover. The Y152F/S185G SbnA double mutant was completely inactive and its crystal structure revealed that the mutations induced a closed form of the enzyme in the absence of the alpha-aminoacrylate intermediate. Lastly, L-cysteine was shown to be a competitive inhibitor of SbnA by forming a non-productive external aldimine with the PLP cofactor. These results suggest a regulatory link between siderophore and L-cysteine biosynthesis, revealing a potential mechanism to reduce iron uptake under oxidative stress. Deciphering the Substrate Specificity of SbnA, the Enzyme Catalyzing the First Step in Staphyloferrin B Biosynthesis.,Kobylarz MJ, Grigg JC, Liu Y, Lee MS, Heinrichs DE, Murphy ME Biochemistry. 2016 Jan 21. PMID:26794841 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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