8c5n

Sub-atomic resolution structure of the chitin-binding protein D (CbpD) from Pseudomonas aeruginosa

spinqualitylabelsall models 8c5n, resolution 0.75Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8c5n is a 1 chain structure with sequence from Pseudomonas aeruginosa PA14. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 0.75Å Ligands: CL Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Pseudomonas aeruginosa (PA) CbpD belongs to the lytic polysaccharide monooxygenases (LPMOs), a family of enzymes that cleave chitin or related polysaccharides. Here, we demonstrate a virulence role of CbpD in PA pneumonia linked to impairment of host complement function and opsonophagocytic clearance. Following intratracheal challenge, a PA DeltaCbpD mutant was more easily cleared and produced less mortality than the wild-type parent strain. The x-ray crystal structure of the CbpD LPMO domain was solved to subatomic resolution (0.75A) and its two additional domains modeled by small-angle X-ray scattering and Alphafold2 machine-learning algorithms, allowing structure-based immune epitope mapping. Immunization of naive mice with recombinant CbpD generated high IgG antibody titers that promoted human neutrophil opsonophagocytic killing, neutralized enzymatic activity, and protected against lethal PA pneumonia and sepsis. IgG antibodies generated against full-length CbpD or its noncatalytic M2+CBM73 domains were opsonic and protective, even in previously PA-exposed mice, while antibodies targeting the AA10 domain were not. Preexisting antibodies in PA-colonized cystic fibrosis patients primarily target the CbpD AA10 catalytic domain. Further exploration of LPMO family proteins, present across many clinically important and antibiotic-resistant human pathogens, may yield novel and effective vaccine antigens. Immunization with lytic polysaccharide monooxygenase CbpD induces protective immunity against Pseudomonas aeruginosa pneumonia.,Askarian F, Tsai CM, Cordara G, Zurich RH, Bjanes E, Golten O, Vinther Sorensen H, Kousha A, Meier A, Chikwati E, Bruun JA, Ludviksen JA, Choudhury B, Trieu D, Davis S, Edvardsen PKT, Mollnes TE, Liu GY, Krengel U, Conrad DJ, Vaaje-Kolstad G, Nizet V Proc Natl Acad Sci U S A. 2023 Jul 25;120(30):e2301538120. doi: , 10.1073/pnas.2301538120. Epub 2023 Jul 17. PMID:37459522 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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