7MHW
Crystal structure of the protease inhibitor U-Omp19 from Brucella abortus fused to Maltose-binding protein
Summary for 7MHW
Entry DOI | 10.2210/pdb7mhw/pdb |
Descriptor | Maltose/maltodextrin-binding periplasmic protein,Outer membrane lipoprotein omp19, SULFATE ION (3 entities in total) |
Functional Keywords | protease inhibitor, mbp-fusion protein, membrane protein |
Biological source | Escherichia coli More |
Total number of polymer chains | 1 |
Total formula weight | 52406.68 |
Authors | Darriba, M.L.,Klinke, S.,Otero, L.H.,Cerutti, M.L.,Cassataro, J.,Pasquevich, K.A. (deposition date: 2021-04-15, release date: 2022-04-20, Last modification date: 2024-10-23) |
Primary citation | Laura Darriba, M.,Castro, C.P.,Coria, L.M.,Bruno, L.,Laura Cerutti, M.,Otero, L.H.,Chemes, L.B.,Rasia, R.M.,Klinke, S.,Cassataro, J.,Pasquevich, K.A. A disordered region retains the full protease inhibitor activity and the capacity to induce CD8 + T cells in vivo of the oral vaccine adjuvant U-Omp19. Comput Struct Biotechnol J, 20:5098-5114, 2022 Cited by PubMed Abstract: U-Omp19 is a bacterial protease inhibitor from that inhibits gastrointestinal and lysosomal proteases, enhancing the half-life and immunogenicity of co-delivered antigens. U-Omp19 is a novel adjuvant that is in preclinical development with various vaccine candidates. However, the molecular mechanisms by which it exerts these functions and the structural elements responsible for these activities remain unknown. In this work, a structural, biochemical, and functional characterization of U-Omp19 is presented. Dynamic features of U-Omp19 in solution by NMR and the crystal structure of its C-terminal domain are described. The protein consists of a compact C-terminal beta-barrel domain and a flexible N-terminal domain. The latter domain behaves as an intrinsically disordered protein and retains the full protease inhibitor activity against pancreatic elastase, papain and pepsin. This domain also retains the capacity to induce CD8 T cells of U-Omp19. This information may lead to future rationale vaccine designs using U-Omp19 as an adjuvant to deliver other proteins or peptides in oral formulations against infectious diseases, as well as to design strategies to incorporate modifications in its structure that may improve its adjuvanticity. PubMed: 36187929DOI: 10.1016/j.csbj.2022.08.054 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (2.55 Å) |
Structure validation
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