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@PHDTHESIS{Sommer:638196,
      author       = {Sommer, Max},
      title        = {{S}tructural and {F}unctional {I}nsightsinto {S}tm{P}r1:
                      {S}tenotrophomonasmaltophilia’s {M}ain {V}irulence
                      {F}actor},
      school       = {University of Hamburg},
      type         = {Dissertation},
      reportid     = {PUBDB-2025-04014},
      pages        = {1-170},
      year         = {2025},
      note         = {Dissertation, University of Hamburg, 2025},
      abstract     = {With the increasing prevalence of antimicrobial resistance
                      (AMR), a pressing globalhealth crisis is emerging,
                      significantly contributing to rising mortality
                      ratesworldwide. The excessive and improper use of
                      antibiotics in both human medicineand agriculture, coupled
                      with insufficient regulation and the global spread
                      ofresistant pathogens, accelerate the development of
                      multidrug-resistant bacteriasuch as Stenotrophomonas
                      maltophilia. This dissertation focuses on the structuraland
                      biochemical characterization of StmPr1, a secreted serine
                      protease involvedin the virulence and persistence of S.
                      maltophilia. Through a combination of X-raycrystallography,
                      small-angle X-ray scattering (SAXS), and molecular
                      dynamics(MD) simulations, the structures of the 36 kDa and
                      47 kDa forms of StmPr1 wereelucidated. These studies
                      provided key insights into the structural states
                      andcatalytic mechanisms of StmPr1.A major focus of this
                      dissertation was the structural analysis of StmPr1,
                      withparticular attention to differences between the two
                      forms in terms of substratespecificity and binding mode. In
                      addition to the internal differences of StmPr1, theactivity
                      of boronic acid derivatives as potential inhibitors was
                      investigated, as theseare known for their inhibitory effects
                      on serine proteases, particularly asproteasome inhibitors.
                      Furthermore, molecular docking and dynamics simulationswere
                      employed to identify additional potential inhibitors.These
                      bioinformatics findings, in combination with classical
                      structural analyses,shed new light on the role of StmPr1 in
                      the survival and adaptation of S. maltophilia.As such, the
                      results contribute to a better understanding of bacterial
                      proteases aspromising therapeutic targets, particularly in
                      the context of AMR. Moreover, thesuccessful crystallization
                      and subsequent structural characterization using
                      state-17of-the-art methods provide a foundation for future
                      studies, with the potential goalof developing an inhibitor
                      that could aid in the treatment of S. maltophilia
                      infections.By integrating structural bioinformatics,
                      classical X-ray structural analysis, andestablished methods
                      in structural biology and biochemistry, this dissertation
                      laysthe groundwork for a deeper understanding of StmPr1
                      specifically and bacterialproteases in general. This
                      approach offers a basis for innovative inhibitor
                      designstrategies and is of significant relevance in the
                      fight against infections caused bymultidrug-resistant
                      bacteria.},
      cin          = {EMBL-User},
      cid          = {I:(DE-H253)EMBL-User-20120814},
      pnm          = {6G3 - PETRA III (DESY) (POF4-6G3)},
      pid          = {G:(DE-HGF)POF4-6G3},
      experiment   = {EXP:(DE-H253)P-P12-20150101 / EXP:(DE-H253)P-P11-20150101 /
                      EXP:(DE-H253)P-P13-20150101},
      typ          = {PUB:(DE-HGF)11},
      url          = {https://bib-pubdb1.desy.de/record/638196},
}