8XFA

Structure of the siderophore periplasmic binding protein FtsB mutant Y137A from Streptococcus pyogenes with ferrioxamine E bound

8XFA の概要

• エントリーDOI: 10.2210/pdb8xfa/pdb
• 分子名称: Iron-hydroxamate ABC transporter substrate-binding protein FtsB, (8E)-6,17,28-trihydroxy-1,6,12,17,23,28-hexaazacyclotritriacont-8-ene-2,5,13,16,24,27-hexone, FE (III) ION, ... (5 entities in total)
• 機能のキーワード: streptococcus pyogenes, siderophore, hydroxamate, ftsb, abc transporter, alanine scanning, antibiotic strategy, ferrioxamine e, metal binding protein
• 由来する生物種: Streptococcus pyogenes SSI-1
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 32504.02

構造登録者

Caaveiro, J.M.M.,Fernandez-Perez, J.,Tsumoto, K. (登録日: 2023-12-13, 公開日: 2024-10-09, 最終更新日: 2024-12-18)

主引用文献

Fernandez-Perez, J.,Senoo, A.,Caaveiro, J.M.M.,Nakakido, M.,de Vega, S.,Nakagawa, I.,Tsumoto, K.
Structural basis for the ligand promiscuity of the hydroxamate siderophore binding protein FtsB from Streptococcus pyogenes.
Structure, 32:2410-2421.e3, 2024

PubMed Abstract: Pathogenic bacteria must secure the uptake of nutritional metals such as iron for their growth, making their import systems attractive targets for the development of new antimicrobial modalities. In the pathogenic bacterium Streptococcus pyogenes, the iron uptake system FtsABCD transports iron encapsulated by siderophores of the hydroxamate class. However, the inability of S. pyogenes to produce these metabolites makes the biological and clinical relevance of this route unresolved. Herein, we demonstrated that the periplasmic binding protein FtsB recognizes not only the hydroxamate siderophore ferrichrome, as previously documented, but also ferrioxamine E (FOE), ferrioxamine B (FOB), and bisucaberin (BIS), each of them with high affinity (nM level). Up to seven aromatic residues in the binding pocket accommodate the variable backbones of the different siderophores through CH-π interactions, explaining ligand promiscuity. Collectively, our observations revealed how S. pyogenes exploits the diverse xenosiderophores produced by other microorganisms as iron sources to secure this precious nutrient.

PubMed: 39395422
DOI: 10.1016/j.str.2024.09.018

実験手法

X-RAY DIFFRACTION (1.85 Å)