7CBB

Crystal structure of SbnC in the biosynthesis of staphyloferrin B

Summary for 7CBB

• Entry DOI: 10.2210/pdb7cbb/pdb
• Descriptor: IucA/IucC family siderophore biosynthesis protein, ADENOSINE MONOPHOSPHATE (3 entities in total)
• Functional Keywords: cupped hand fold, type b nis synthetase, siderophore synthetase, biosynthetic protein
• Biological source: Staphylococcus aureus
• Total number of polymer chains: 2
• Total formula weight: 137073.72

Authors

Tang, J.,Ju, Y.,Zhou, H. (deposition date: 2020-06-11, release date: 2020-09-23, Last modification date: 2024-10-23)

Primary citation

Tang, J.,Ju, Y.,Zhou, J.,Guo, J.,Gu, Q.,Xu, J.,Zhou, H.
Structural and Biochemical Characterization of SbnC as a Representative Type B Siderophore Synthetase.
Acs Chem.Biol., 15:2731-2740, 2020

PubMed Abstract: Staphyloferrin B is a key siderophore secreted by to acquire ferric ions from a host during infection, and its biosynthetic pathway has been validated to develop efficient antibacterial agents. Herein, we report the crystal structure of AMP-bound SbnC from (SbnC) as the first representative structure of type B synthetases in the biosynthesis of α-hydroxycarboxylate siderophores. While type B synthetases specifically use α-ketoglutarate (α-KG) as their carboxylic acid substrate, SbnC showed unique structural features in the substrate pocket compared with the type A and C synthetases. Screening of α-KG analogues suggested that the hydrogen-bonding interaction between the α-carbonyl group of α-KG and residue Lys552 is a key determinant for the substrate selectivity of type B synthetases. Interestingly, citrate, the product of the tricarboxylic acid cycle and the substrate of type A synthetases, was found to inhibit the activity of SbnC with an IC value of 83 μM by mimicking α-KG binding, suggesting a potential regulatory role of the tricarboxylic acid cycle, whose activity is under the control of the intracellular iron concentration, to SbnC and other type B synthetases. These results provide critical new information to understand the structure, function, and regulation of type B synthetases in the siderophore-based iron acquisition system employed by a large number of pathogenic microbes.

PubMed: 32880431
DOI: 10.1021/acschembio.0c00523

Experimental method

X-RAY DIFFRACTION (2.6 Å)