9FVE
Crystal structure of VcSiaP W73A mutant in complex with sialic acid and a VHH antibody (VHH_VcP#2)
Summary for 9FVE
| Entry DOI | 10.2210/pdb9fve/pdb |
| Descriptor | Sialic acid-binding periplasmic protein SiaP, VHH_VcP#2, N-acetyl-beta-neuraminic acid, ... (4 entities in total) |
| Functional Keywords | substrate binding protein, sialic acid, trap transporter, vhh antibody, nanobody, complex, transport protein |
| Biological source | Vicugna pacos (alpaca) More |
| Total number of polymer chains | 24 |
| Total formula weight | 573969.44 |
| Authors | Schneberger, N.,Hagelueken, G. (deposition date: 2024-06-26, release date: 2024-11-06, Last modification date: 2024-12-04) |
| Primary citation | Schneberger, N.,Hendricks, P.,Peter, M.F.,Gehrke, E.,Binder, S.C.,Koenig, P.A.,Menzel, S.,Thomas, G.H.,Hagelueken, G. Allosteric substrate release by a sialic acid TRAP transporter substrate binding protein. Commun Biol, 7:1559-1559, 2024 Cited by PubMed Abstract: The tripartite ATP-independent periplasmic (TRAP) transporters enable Vibrio cholerae and Haemophilus influenzae to acquire sialic acid, aiding their colonization of human hosts. This process depends on SiaP, a substrate-binding protein (SBP) that captures and delivers sialic acid to the transporter. We identified 11 nanobodies that bind specifically to the SiaP proteins from H. influenzae (HiSiaP) and V. cholerae (VcSiaP). Two nanobodies inhibited sialic acid binding. Detailed structural and biophysical studies of one nanobody-SBP complex revealed an allosteric inhibition mechanism, preventing ligand binding and releasing pre-bound sialic acid. A hydrophobic surface pocket of the SBP is crucial for the allosteric mechanism and for the conformational rearrangement that occurs upon binding of sialic acid to the SBP. Our findings provide new clues regarding the mechanism of TRAP transporters, as well as potential starting points for novel drug design approaches to starve these human pathogens of important host-derived molecules. PubMed: 39580575DOI: 10.1038/s42003-024-07263-6 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.81 Å) |
Structure validation
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