4epf

The crystal structure of pesticin from Yersinia pestis

spinqualitylabelsall models 4epf, resolution 2.09Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4epf is a 2 chain structure with sequence from Yersinia pestis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. NonStd Res: MSE Related: 4epa, 4epi Gene: pst, YP_pPCP06, YPPCP1.05c (Yersinia pestis) Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed Bacterial pathogens are becoming increasingly resistant to antibiotics. As an alternative therapeutic strategy, phage therapy reagents containing purified viral lysins have been developed against Gram-positive organisms but not against Gram-negative organisms due to the inability of these types of drugs to cross the bacterial outer membrane. We solved the crystal structures of a Yersinia pestis outer membrane transporter called FyuA and a bacterial toxin called pesticin that targets this transporter. FyuA is a beta-barrel membrane protein belonging to the family of TonB dependent transporters, whereas pesticin is a soluble protein with two domains, one that binds to FyuA and another that is structurally similar to phage T4 lysozyme. The structure of pesticin allowed us to design a phage therapy reagent comprised of the FyuA binding domain of pesticin fused to the N-terminus of T4 lysozyme. This hybrid toxin kills specific Yersinia and pathogenic E. coli strains and, importantly, can evade the pesticin immunity protein (Pim) giving it a distinct advantage over pesticin. Furthermore, because FyuA is required for virulence and is more common in pathogenic bacteria, the hybrid toxin also has the advantage of targeting primarily disease-causing bacteria rather than indiscriminately eliminating natural gut flora. Structural engineering of a phage lysin that targets Gram-negative pathogens.,Lukacik P, Barnard TJ, Keller PW, Chaturvedi KS, Seddiki N, Fairman JW, Noinaj N, Kirby TL, Henderson JP, Steven AC, Hinnebusch BJ, Buchanan SK Proc Natl Acad Sci U S A. 2012 Jun 7. PMID:22679291 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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