7XLI
Crystal structure of IsdB linker-NEAT2 bound to a nanobody (VHH)
Summary for 7XLI
Entry DOI | 10.2210/pdb7xli/pdb |
Descriptor | Iron-regulated surface determinant protein B, VHH6 nanobody, CHLORIDE ION, ... (5 entities in total) |
Functional Keywords | isdh system heme staphylococcus aureus vhh nanodoby antimicrobial, metal transport |
Biological source | Staphylococcus aureus subsp. aureus Mu50 More |
Total number of polymer chains | 2 |
Total formula weight | 36220.37 |
Authors | Caaveiro, J.M.M.,Valenciano-Bellido, S.,Tsumoto, K. (deposition date: 2022-04-21, release date: 2023-05-31, Last modification date: 2024-10-30) |
Primary citation | 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 Cited by 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: 37330175DOI: 10.1016/j.jbc.2023.104927 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (1.7 Å) |
Structure validation
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