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http://purl.uniprot.org/citations/37633566http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/37633566http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/37633566http://www.w3.org/2000/01/rdf-schema#comment"Macrophage infectivity potentiator (MIP) proteins are widespread in human pathogens including Legionella pneumophila, the causative agent of Legionnaires' disease and protozoans such as Trypanosoma cruzi. All MIP proteins contain a FKBP (FK506 binding protein)-like prolyl-cis/trans-isomerase domain that hence presents an attractive drug target. Some MIPs such as the Legionella pneumophila protein (LpMIP) have additional appendage domains of mostly unknown function. In full-length, homodimeric LpMIP, the N-terminal dimerization domain is linked to the FKBP-like domain via a long, free-standing stalk helix. Combining X-ray crystallography, NMR and EPR spectroscopy and SAXS, we elucidated the importance of the stalk helix for protein dynamics and inhibitor binding to the FKBP-like domain and bidirectional crosstalk between the different protein regions. The first comparison of a microbial MIP and a human FKBP in complex with the same synthetic inhibitor was made possible by high-resolution structures of LpMIP with a [4.3.1]-aza-bicyclic sulfonamide and provides a basis for designing pathogen-selective inhibitors. Through stereospecific methylation, the affinity of inhibitors to L. pneumophila and T. cruzi MIP was greatly improved. The resulting X-ray inhibitor-complex structures of LpMIP and TcMIP at 1.49 and 1.34 Å, respectively, provide a starting point for developing potent inhibitors against MIPs from multiple pathogenic microorganisms."xsd:string
http://purl.uniprot.org/citations/37633566http://purl.org/dc/terms/identifier"doi:10.1016/j.ijbiomac.2023.126366"xsd:string
http://purl.uniprot.org/citations/37633566http://purl.org/dc/terms/identifier"doi:10.1016/j.ijbiomac.2023.126366"xsd:string
http://purl.uniprot.org/citations/37633566http://purl.uniprot.org/core/author"Guskov A."xsd:string
http://purl.uniprot.org/citations/37633566http://purl.uniprot.org/core/author"Guskov A."xsd:string
http://purl.uniprot.org/citations/37633566http://purl.uniprot.org/core/author"Joseph B."xsd:string
http://purl.uniprot.org/citations/37633566http://purl.uniprot.org/core/author"Joseph B."xsd:string
http://purl.uniprot.org/citations/37633566http://purl.uniprot.org/core/author"Wiedemann C."xsd:string
http://purl.uniprot.org/citations/37633566http://purl.uniprot.org/core/author"Wiedemann C."xsd:string
http://purl.uniprot.org/citations/37633566http://purl.uniprot.org/core/author"Hausch F."xsd:string
http://purl.uniprot.org/citations/37633566http://purl.uniprot.org/core/author"Hausch F."xsd:string
http://purl.uniprot.org/citations/37633566http://purl.uniprot.org/core/author"Whittaker J.J."xsd:string
http://purl.uniprot.org/citations/37633566http://purl.uniprot.org/core/author"Whittaker J.J."xsd:string
http://purl.uniprot.org/citations/37633566http://purl.uniprot.org/core/author"Dajka M."xsd:string
http://purl.uniprot.org/citations/37633566http://purl.uniprot.org/core/author"Dajka M."xsd:string
http://purl.uniprot.org/citations/37633566http://purl.uniprot.org/core/author"Goretzki B."xsd:string
http://purl.uniprot.org/citations/37633566http://purl.uniprot.org/core/author"Goretzki B."xsd:string
http://purl.uniprot.org/citations/37633566http://purl.uniprot.org/core/author"Harder J.M."xsd:string
http://purl.uniprot.org/citations/37633566http://purl.uniprot.org/core/author"Harder J.M."xsd:string
http://purl.uniprot.org/citations/37633566http://purl.uniprot.org/core/author"Hellmich U.A."xsd:string
http://purl.uniprot.org/citations/37633566http://purl.uniprot.org/core/author"Hellmich U.A."xsd:string
http://purl.uniprot.org/citations/37633566http://purl.uniprot.org/core/author"Krajczy P.R."xsd:string
http://purl.uniprot.org/citations/37633566http://purl.uniprot.org/core/author"Krajczy P.R."xsd:string