6JB5
Crystal structure of nanobody D3-L11 mutant Y102A in complex with hen egg-white lysozyme (form II)
Summary for 6JB5
| Entry DOI | 10.2210/pdb6jb5/pdb |
| Descriptor | Nanobody D3-L11, Lysozyme C, CHLORIDE ION, ... (5 entities in total) |
| Functional Keywords | nanobody, hot-spot mutagenesis, thermodynamics, biomolecular recognition, immune system, immune system-hydrolase complex, immune system/hydrolase |
| Biological source | Camelus dromedarius More |
| Total number of polymer chains | 2 |
| Total formula weight | 29403.37 |
| Authors | Caaveiro, J.M.M.,Tamura, H.,Akiba, H.,Tsumoto, K. (deposition date: 2019-01-25, release date: 2019-11-06, Last modification date: 2024-10-23) |
| Primary citation | Akiba, H.,Tamura, H.,Kiyoshi, M.,Yanaka, S.,Sugase, K.,Caaveiro, J.M.M.,Tsumoto, K. Structural and thermodynamic basis for the recognition of the substrate-binding cleft on hen egg lysozyme by a single-domain antibody. Sci Rep, 9:15481-15481, 2019 Cited by PubMed Abstract: Single-domain antibodies (VHHs or nanobodies), developed from heavy chain-only antibodies of camelids, are gaining attention as next-generation therapeutic agents. Despite their small size, the high affinity and specificity displayed by VHHs for antigen molecules rival those of IgGs. How such small antibodies achieve that level of performance? Structural studies have revealed that VHHs tend to recognize concave surfaces of their antigens with high shape-complementarity. However, the energetic contribution of individual residues located at the binding interface has not been addressed in detail, obscuring the actual mechanism by which VHHs target the concave surfaces of proteins. Herein, we show that a VHH specific for hen egg lysozyme, D3-L11, not only displayed the characteristic binding of VHHs to a concave region of the surface of the antigen, but also exhibited a distribution of energetic hot-spots like those of IgGs and conventional protein-protein complexes. The highly preorganized and energetically compact interface of D3-L11 recognizes the concave epitope with high shape complementarity by the classical lock-and-key mechanism. Our results shed light on the fundamental basis by which a particular VHH accommodate to the concave surface of an antigens with high affinity in a specific manner, enriching the mechanistic landscape of VHHs. PubMed: 31664051DOI: 10.1038/s41598-019-50722-y PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.55 Å) |
Structure validation
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