9BLJ
Crystal structure of a serine protease inhibitor HPI from Hevea brasiliensis
Summary for 9BLJ
| Entry DOI | 10.2210/pdb9blj/pdb |
| Descriptor | Protease inhibitor HPI (2 entities in total) |
| Functional Keywords | serine protease inhibitor, plant protein |
| Biological source | Hevea brasiliensis (rubber tree) |
| Total number of polymer chains | 1 |
| Total formula weight | 7747.80 |
| Authors | |
| Primary citation | Terron-Hernandez, J.,Gomez-Velasco, H.,Pinzon-Yaya, L.,Hernandez-Santoyo, A.,Garcia-Ramirez, B.,Rodriguez-Romero, A. Understanding the structure and function of HPI, a rubber tree serine protease inhibitor, and its interaction with subtilisin. Biochem.Biophys.Res.Commun., 763:151801-151801, 2025 Cited by PubMed Abstract: Protease inhibitors are crucial in regulating enzymatic activity and have extensive applications in medicine, biotechnology, and agriculture. This study characterizes a recombinant protease inhibitor from Hevea brasiliensis (rHPI), highlighting its unique structural features and inhibitory potential. Using Matrix-Assisted Laser Desorption/Ionization (MALDI) analysis, the inhibitor exhibits one distinct peak around 7.54 kDa. Enzymatic assays using N-succinyl-Ala-Ala-Pro-Phe-p-nitroanilide as a substrate confirmed the inhibitor's activity against subtilisin Carlsberg, a widely utilized serine protease in industry and biotechnology. The crystal structure of rHPI, resolved at 1.73 Å, reveals a topology closely resembling eglin c, including a single alpha-helix, two parallel beta-strands, and a distinctive binding loop spanning residues 40-51. Disordered regions at the N- and C-termini contribute to its structural uniqueness. Despite lacking disulfide bonds and featuring an Arg residue instead of Trp at the P' position, rHPI maintains a high affinity for subtilisin. Isothermal titration calorimetry (ITC) showed that this interaction is entropically driven. Molecular docking and dynamics simulations of the rHPI-subtilisin complex revealed the formation of antiparallel β-sheets, hydrogen bonding involving the protein backbone, and a salt bridge between His64 of subtilisin and Asp47 of rHPI. These findings provide valuable insights into the molecular basis of rHPI's inhibitory activity and offer a framework for the rational design of novel subtilisin inhibitors with potential applications in agricultural and industrial settings. PubMed: 40233429DOI: 10.1016/j.bbrc.2025.151801 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.74 Å) |
Structure validation
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