3QG6

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

Summary for 3QG6

• Entry DOI: 10.2210/pdb3qg6/pdb
• Related: 3QG7
• Descriptor: AP4-24H11 Light Chain, AP4-24H11 Heavy Chain, Agr autoinducing peptide, ... (6 entities in total)
• Functional Keywords: immunoglobulin fold, antigen binding, aip4 binding, secreted, immune system-inhibitor complex, immune system/inhibitor
• Biological source: Mus musculus (mouse); More
• Total number of polymer chains: 6
• Total formula weight: 97059.93

Authors

Kirchdoerfer, R.N.,Janda, J.D.,Kaufmann, G.F.,Wilson, I.A. (deposition date: 2011-01-24, release date: 2011-03-23, Last modification date: 2023-09-13)

Primary citation

Kirchdoerfer, R.N.,Garner, A.L.,Flack, C.E.,Mee, J.M.,Horswill, A.R.,Janda, K.D.,Kaufmann, G.F.,Wilson, I.A.
Structural Basis for Ligand Recognition and Discrimination of a Quorum-quenching Antibody.
J.Biol.Chem., 286:17351-17358, 2011

PubMed Abstract: 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 Å 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.

PubMed: 21454495
DOI: 10.1074/jbc.M111.231258

Experimental method

X-RAY DIFFRACTION (2.5 Å)