8 research outputs found
Conformation of the adenylate cyclase toxin of Bordetella pertussis.
Tato práce se zabĂ˝vá uspořádánĂm RTX ("Repeats in ToXin") domĂ©n vybranĂ˝ch RTX toxinĹŻ a vlivem tÄ›chto struktur pĹ™edevšĂm na balenĂ toxinĹŻ do nativnĂ struktury jejich sekreci a. Pro strukturnĂ analĂ˝zu byly vybrány RTX domĂ©ny ApxI (Actinobacillus pleuropneumoniae-RTX- toxin I) z bakterie Actinobacillus pleuropneumoniae, HlyA (Alfa-hemolysin) z bakterie Escherichia coli a LtxA (Leukotoxin A) z bakterie Aggregatibacter actinomycetemcomitans a bloky 4 a 5 RTX domĂ©ny CyaA (adenylátcyklázovĂ˝ toxin) z bakterie Bordetella pertussis. PodaĹ™ilo se zĂskat a charakterizovat struktury RTX domĂ©ny Ltxa A a RTX bloky 5 a 4-5 CyaA. Na základÄ› SAXS (maloĂşhlovĂ˝ RTG rozptyl) modelu, dĹ™Ăve vyĹ™ešenĂ˝ch struktur RTX proteinĹŻ a zde prezentovanĂ˝ch struktur byly vytvoĹ™eny dva modely celĂ© rozsáhlĂ© RTX domĂ©ny CyaA.This work is focused on the RTX (Repeats in ToXin) domains structure of selected RTX toxins and its impact on secretion and protein folding. The structural analysis included RTX domains of ApxI (Actinobacillus pleuropneumoniae-RTX-toxin I) from Actinobacillus pleuropneumoniae, HlyA (Alfa-hemolysin) from Escherichia coli and LtxA (Leukotoxin A) from Aggregatibacter actinomycetemcomitans and blocs 4 a 5 RTX domain CyaA (adenylate cyclase toxin) from Bordetella pertussis. The structures of LtxA RTX domain and CyaA RTX blocs 4 and 5 were obtained and characterized. Two models of CyaA RTX domain were built based on SAXS (Small Angle X-ray Scattering) model, previously solved RTX structures and RTX structures presented here.Department of Genetics and MicrobiologyKatedra genetiky a mikrobiologieFaculty of SciencePĹ™ĂrodovÄ›decká fakult
Conformation of the adenylate cyclase toxin of Bordetella pertussis.
This work is focused on the RTX (Repeats in ToXin) domains structure of selected RTX toxins and its impact on secretion and protein folding. The structural analysis included RTX domains of ApxI (Actinobacillus pleuropneumoniae-RTX-toxin I) from Actinobacillus pleuropneumoniae, HlyA (Alfa-hemolysin) from Escherichia coli and LtxA (Leukotoxin A) from Aggregatibacter actinomycetemcomitans and blocs 4 a 5 RTX domain CyaA (adenylate cyclase toxin) from Bordetella pertussis. The structures of LtxA RTX domain and CyaA RTX blocs 4 and 5 were obtained and characterized. Two models of CyaA RTX domain were built based on SAXS (Small Angle X-ray Scattering) model, previously solved RTX structures and RTX structures presented here
Stationary phase in Bacillus subtilis
Department of Genetics and MicrobiologyKatedra genetiky a mikrobiologieFaculty of SciencePĹ™ĂrodovÄ›decká fakult
Conformation of the adenylate cyclase toxin of Bordetella pertussis.
This work is focused on the RTX (Repeats in ToXin) domains structure of selected RTX toxins and its impact on secretion and protein folding. The structural analysis included RTX domains of ApxI (Actinobacillus pleuropneumoniae-RTX-toxin I) from Actinobacillus pleuropneumoniae, HlyA (Alfa-hemolysin) from Escherichia coli and LtxA (Leukotoxin A) from Aggregatibacter actinomycetemcomitans and blocs 4 a 5 RTX domain CyaA (adenylate cyclase toxin) from Bordetella pertussis. The structures of LtxA RTX domain and CyaA RTX blocs 4 and 5 were obtained and characterized. Two models of CyaA RTX domain were built based on SAXS (Small Angle X-ray Scattering) model, previously solved RTX structures and RTX structures presented here
Adenylate cyclase toxin of Bordetella pertussis, its conformation and ion balance in host cell.
Adenylate cyclase (CyaA, ACT) toxin is one of the major virulence factors of Bordetella pertussis. Although CyaA binds to many types of membranes, it is assumed that the integrin CD11b/CD18 is its receptor which is expressed on the surface of myeloid cells. CyaA belongs to the family of RTX toxin-hemolysins. CyaA acts on the host cells by two independent activities. One of them is the conversion of ATP to cyclic AMP, which is catalyzed by adenylate cyclase (AC) domain after its translocation into the cytosol of the host cell, which leads to the entry of calcium cations into the host cell. Translocation is probably initiated by interaction of CyaA monomer with the target membrane. The second activity is the formation of CyaA channel selective for cations, which probably causes colloid osmotic lysis of target cells. The channel forming activity is provided by RTX hemolysin domain which most probably forms oligomers, although it was found that CyaA as a monomer causes leakage of potassium cations from the host cell. It is also not clear whether the oligomerization of CyaA would occur in solution, or after interaction with the host membrane. The aim of this study was to examine the flow of sodium ions on the membrane of murine macrophages J774A.1, which express integrin CD11b/CD18 on their surface...
Development of PSMA-1007-Related Series of 18 F-Labeled Glu-Ureido-Type PSMA Inhibitors
In recent years, a number of drugs targeting the prostate-specific membrane antigen (PSMA) have become important tools in the diagnosis and treatment of prostate cancer. In the present work, we report on the synthesis and preclinical evaluation of a series of F-labeled PSMA ligands for diagnostic application based on the theragnostic ligand PSMA-617. By applying modifications to the linker structure, insight into the structure–activity relationship could be gained, highlighting the importance of hydrophilicity and stereoselectivity on interaction with PSMA and hence the biodistribution. Selected compounds were co-crystallized with the PSMA protein and analyzed by X-rays with mixed results. Among these, PSMA-1007 (compound 5) showed the best interaction with the PSMA protein. The respective radiotracer [F]PSMA-1007 was translated into the clinic and is, in the meantime, subject of advanced clinical trials
Development of PSMA 1007 Related Series of F 18 Labeled Glu Ureido Type PSMA Inhibitors
In recent years, a number of drugs targeting the prostate-specific membrane antigen (PSMA) have become important tools in the diagnosis and treatment of prostate cancer. In the present work, we report on the synthesis and preclinical evaluation of a series of F-labeled PSMA ligands for diagnostic application based on the theragnostic ligand PSMA-617. By applying modifications to the linker structure, insight into the structure–activity relationship could be gained, highlighting the importance of hydrophilicity and stereoselectivity on interaction with PSMA and hence the biodistribution. Selected compounds were co-crystallized with the PSMA protein and analyzed by X-rays with mixed results. Among these, PSMA-1007 (compound 5) showed the best interaction with the PSMA protein. The respective radiotracer [F]PSMA-1007 was translated into the clinic and is, in the meantime, subject of advanced clinical trials