9ULP

Crystal structure of FtsB from Streptococcus pyogenes in complex with Nb1 nanobody

9ULP の概要

• エントリーDOI: 10.2210/pdb9ulp/pdb
• 分子名称: Iron-hydroxamate ABC transporter substrate-binding protein, VHH (3 entities in total)
• 機能のキーワード: vhh, ftsb, iron acquisition, siderophore, anti-bacterial strategy, immune system
• 由来する生物種: Streptococcus pyogenes; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 90723.03

構造登録者

Fernandez-Perez, J.,Caaveiro, J.M.M.,Tsumoto, K. (登録日: 2025-04-20, 公開日: 2026-03-25)

主引用文献

Fernandez-Perez, J.,de Vega, S.,Caaveiro, J.M.M.,Nakakido, M.,Nagatoishi, S.,Senoo, A.,Tanoi, K.,Nozawa, T.,Nakagawa, I.,Tsumoto, K.
Development of an inhibitory monoclonal nanobody targeting Streptococcus pyogenes siderophore binding protein FtsB.
J.Biol.Chem., 302:111224-111224, 2026

PubMed Abstract: Due to the limited availability of metals inside the human body, pathogenic bacteria must produce multiple highly specialized metal transporters to cause infection. These transporters constitute attractive targets for developing novel antibacterial strategies. Streptococcus pyogenes possesses three iron transporters, of which the FtsABCD system is specialized in the uptake of ferric hydroxamates. The role of this transporter in infection remains unclear. In this study, we developed a monoclonal alpaca VHH, or nanobody, Nb1, targeting FtsB. Nb1 binds to FtsB with sub-nM affinity, in an enthalpy-driven manner, and with a characteristically slow dissociation rate. Solvent accessibility analysis by hydrogen/deuterium exchange coupled with mass spectrometry, mutational analyses, and X-ray crystallography revealed that the epitope of Nb1 is in the binding pocket of FtsB. The nanobody competitively inhibited the binding of multiple hydroxamate siderophores and partially inhibited the uptake of siderophores in S. pyogenes cells. The inhibitory activity of Nb1 on siderophore transport represents a new tool to study the role of the FtsABCD transporter and can be used as a potential inhibitor of S. pyogenes growth under iron-limited conditions.

PubMed: 41651419
DOI: 10.1016/j.jbc.2026.111224

実験手法

X-RAY DIFFRACTION (2.55 Å)