9ULP
Crystal structure of FtsB from Streptococcus pyogenes in complex with Nb1 nanobody
Summary for 9ULP
| Entry DOI | 10.2210/pdb9ulp/pdb |
| Descriptor | Iron-hydroxamate ABC transporter substrate-binding protein, VHH (3 entities in total) |
| Functional Keywords | vhh, ftsb, iron acquisition, siderophore, anti-bacterial strategy, immune system |
| Biological source | Streptococcus pyogenes More |
| Total number of polymer chains | 4 |
| Total formula weight | 90723.03 |
| Authors | Fernandez-Perez, J.,Caaveiro, J.M.M.,Tsumoto, K. (deposition date: 2025-04-20, release date: 2026-03-25) |
| Primary citation | 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 Cited by 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: 41651419DOI: 10.1016/j.jbc.2026.111224 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.55 Å) |
Structure validation
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