7t82

Crystal Structure of LEUKOCIDIN E/CENTYRIN S26/FAB B438

spinqualitylabelsall models 7t82, resolution 3.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7t82 is a 8 chain structure with sequence from Mus musculus, Staphylococcaceae and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.5Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function LUKEV_STAA8 Part of a bi-component leucotoxin that acts by forming pores in the membrane of the target cells. The activity of LukEv-LukDv to rabbit leukocytes is similar to that of the Panton-Valentine leucocidin (PVL). LukEv-LukDv is hemolytic to rabbit red blood cells although the activity is only 8% of gamma-hemolysin. Publication Abstract from PubMed Treating and preventing infections by antimicrobial-resistant bacterial pathogens is a worldwide problem. Pathogens such as Staphylococcus aureus produce an array of virulence determinants, making it difficult to identify single targets for the development of vaccines or monoclonal therapies. We described a human-derived anti-S. aureus monoclonal antibody (mAb)-centyrin fusion protein ("mAbtyrin") that simultaneously targets multiple bacterial adhesins, resists proteolysis by bacterial protease GluV8, avoids Fc engagement by S. aureus IgG-binding proteins SpA and Sbi, and neutralizes pore-forming leukocidins via fusion with anti-toxin centyrins, while maintaining Fc- and complement-mediated functions. Compared with the parental mAb, mAbtyrin protected human phagocytes and boosted phagocyte-mediated killing. The mAbtyrin also reduced pathology, reduced bacterial burden, and protected from different types of infections in preclinical animal models. Finally, mAbtyrin synergized with vancomycin, enhancing pathogen clearance in an animal model of bacteremia. Altogether, these data establish the potential of multivalent mAbs for treating and preventing S. aureus diseases. Multivalent human antibody-centyrin fusion protein to prevent and treat Staphylococcus aureus infections.,Buckley PT, Chan R, Fernandez J, Luo J, Lacey KA, DuMont AL, O'Malley A, Brezski RJ, Zheng S, Malia T, Whitaker B, Zwolak A, Payne A, Clark D, Sigg M, Lacy ER, Kornilova A, Kwok D, McCarthy S, Wu B, Morrow B, Nemeth-Seay J, Petley T, Wu S, Strohl WR, Lynch AS, Torres VJ Cell Host Microbe. 2023 May 10;31(5):751-765.e11. doi: , 10.1016/j.chom.2023.04.004. Epub 2023 Apr 24. PMID:37098341 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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