7MHW

Crystal structure of the protease inhibitor U-Omp19 from Brucella abortus fused to Maltose-binding protein

7MHW の概要

• エントリーDOI: 10.2210/pdb7mhw/pdb
• 分子名称: Maltose/maltodextrin-binding periplasmic protein,Outer membrane lipoprotein omp19, SULFATE ION (3 entities in total)
• 機能のキーワード: protease inhibitor, mbp-fusion protein, membrane protein
• 由来する生物種: Escherichia coli; 詳細
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 52406.68

構造登録者

Darriba, M.L.,Klinke, S.,Otero, L.H.,Cerutti, M.L.,Cassataro, J.,Pasquevich, K.A. (登録日: 2021-04-15, 公開日: 2022-04-20, 最終更新日: 2024-10-23)

主引用文献

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

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: 36187929
DOI: 10.1016/j.csbj.2022.08.054

実験手法

X-RAY DIFFRACTION (2.55 Å)