9I6C

StmPr1, Stenotrophomonas maltophilia Protease 1, 36 kDa alkine serine protease in complex with Leupeptin

Summary for 9I6C

• Entry DOI: 10.2210/pdb9i6c/pdb
• Descriptor: Alkaline serine protease, Leupeptin, CALCIUM ION, ... (6 entities in total)
• Functional Keywords: alkaline serine protease, native, excreted protease, subtilisin-like, hydrolase
• Biological source: Stenotrophomonas maltophilia; More
• Total number of polymer chains: 2
• Total formula weight: 37256.84

Authors

Sommer, M.,Outzen, L.,Negm, A.,Windhorst, S.,Weber, W.,Betzel, C. (deposition date: 2025-01-29, release date: 2025-08-06)

Primary citation

Sommer, M.,Negm, A.,Outzen, L.,Windhorst, S.,Gabdulkhakov, A.,Weber, W.,Betzel, C.
Unveiling the structure, function and dynamics of StmPr1 in Stenotrophomonas maltophilia virulence.
Sci Rep, 15:20193-20193, 2025

PubMed Abstract: The increase in infections caused by multi-resistant Gram-negative bacteria, like Stenotrophomonas maltophilia, has become a growing health crisis worldwide. S. maltophilia poses a risk because of its tendency to opportunistically infecting patience for example through colonization of catheters in hospital environments using its intrinsic resistance against multiple antibiotics. Through the COVID-19 pandemic it gained more prominence by being a key pathogen in respiratory co-infections. This study will present a structural analysis of StmPr1, S. maltophilia's main virulence factor, an excreted serine protease. Our study outline structure and functional aspects of StmPr1, revealing a unique autoproteolytic activity resulting in a shortened version of the active enzyme. We also investigated the potential of two groups of peptide-based inhibitors, one being acetyl- and the other being boron-based inhibitors. The focus here lies on Bortezomib, a boron-based serine protease inhibitor, and its potential therapeutic use against S. maltophilia. We provide a structure-function analysis which includes X-ray crystallography data with resolutions ranging from 1.64 to 2.08 Å, molecular dynamic simulations and small-angle X-ray scattering (SAXS) experiments. These data provide a deeper understanding of StmPr1's resilience and mechanisms, while highlighting the relevance of StmPr1's C-terminal extension for correct folding and its stability. Moreover, it also shows that StmPr1 is promising target for further drug discovery investigations to identify compounds and drugs to treat S. maltophilia infections.

PubMed: 40542111
DOI: 10.1038/s41598-025-06177-5

Experimental method

X-RAY DIFFRACTION (2.08 Å)