7XLI

Crystal structure of IsdB linker-NEAT2 bound to a nanobody (VHH)

7XLI の概要

• エントリーDOI: 10.2210/pdb7xli/pdb
• 分子名称: Iron-regulated surface determinant protein B, VHH6 nanobody, CHLORIDE ION, ... (5 entities in total)
• 機能のキーワード: isdh system heme staphylococcus aureus vhh nanodoby antimicrobial, metal transport
• 由来する生物種: Staphylococcus aureus subsp. aureus Mu50; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 36220.37

構造登録者

Caaveiro, J.M.M.,Valenciano-Bellido, S.,Tsumoto, K. (登録日: 2022-04-21, 公開日: 2023-05-31, 最終更新日: 2024-10-30)

主引用文献

Valenciano-Bellido, S.,Caaveiro, J.M.M.,Nakakido, M.,Kuroda, D.,Aikawa, C.,Nakagawa, I.,Tsumoto, K.
Targeting hemoglobin receptors IsdH and IsdB of Staphylococcus aureus with a single VHH antibody inhibits bacterial growth.
J.Biol.Chem., 299:104927-104927, 2023

PubMed Abstract: Methicillin-resistant Staphylococcus aureus, or MRSA, is one of the major causative agents of hospital-acquired infections worldwide. Novel antimicrobial strategies efficient against antibiotic-resistant strains are necessary and not only against S. aureus. Among those, strategies that aim at blocking or dismantling proteins involved in the acquisition of essential nutrients, helping the bacteria to colonize the host, are intensively studied. A major route for S. aureus to acquire iron from the host organism is the Isd (iron surface determinant) system. In particular, the hemoglobin receptors IsdH and IsdB located on the surface of the bacterium are necessary to acquire the heme moiety containing iron, making them a plausible antibacterial target. Herein, we obtained an antibody of camelid origin that blocked heme acquisition. We determined that the antibody recognized the heme-binding pocket of both IsdH and IsdB with nanomolar order affinity through its second and third complementary-determining regions. The mechanism explaining the inhibition of acquisition of heme in vitro could be described as a competitive process in which the complementary-determining region 3 from the antibody blocked the acquisition of heme by the bacterial receptor. Moreover, this antibody markedly reduced the growth of three different pathogenic strains of MRSA. Collectively, our results highlight a mechanism for inhibiting nutrient uptake as an antibacterial strategy against MRSA.

PubMed: 37330175
DOI: 10.1016/j.jbc.2023.104927

実験手法

X-RAY DIFFRACTION (1.7 Å)