3qg7

Structural Basis for Ligand Recognition and Discrimination of a Quorum Quenching Antibody

spinqualitylabelsall models 3qg7, resolution 2.78Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3qg7 is a 2 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: NA, P6G Related: 3qg6 Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed In the postantibiotic era, available treatment options for severe bacterial infections caused by methicillin-resistant Staphylococcus aureus have become limited. Therefore, new and innovative approaches are needed to combat such life-threatening infections. Virulence factor expression in S. aureus is regulated in a cell density-dependent manner using "quorum sensing," which involves generation and secretion of autoinducing peptides (AIPs) into the surrounding environment to activate a bacterial sensor kinase at a particular threshold concentration. Mouse monoclonal antibody AP4-24H11 was shown previously to blunt quorum sensing-mediated changes in gene expression in vitro and protect mice from a lethal dose of S. aureus by sequestering the AIP signal. We have elucidated the crystal structure of the AP4-24H11 Fab in complex with AIP-4 at 2.5 A resolution to determine its mechanism of ligand recognition. A key Glu(H95) provides much of the binding specificity through formation of hydrogen bonds with each of the four amide nitrogens in the AIP-4 macrocyclic ring. Importantly, these structural data give clues as to the interactions between the cognate staphylococcal AIP receptors AgrC and the AIPs, as AP4-24H11.AIP-4 binding recapitulates features that have been proposed for AgrC-AIP recognition. Additionally, these structural insights may enable the engineering of AIP cross-reactive antibodies or quorum quenching vaccines for use in active or passive immunotherapy for prevention or treatment of S. aureus infections. Structural Basis for Ligand Recognition and Discrimination of a Quorum-quenching Antibody.,Kirchdoerfer RN, Garner AL, Flack CE, Mee JM, Horswill AR, Janda KD, Kaufmann GF, Wilson IA J Biol Chem. 2011 May 13;286(19):17351-8. Epub 2011 Mar 23. PMID:21454495 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Antibody

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