The University of Texas System

Emanuel Smeds

Magnus A Hook

Ya-Ping Ko

Vannakambadi K Ganesh

The present invention discloses crystal structure ofClumping factor A (ClfA) in complex with fibrinogen (Fg) derived peptide. Also, the present invention also discloses the use of this structure in the design of ClfA targeted vaccines and therapeutic agents (including monoclonal antibodies). In addition, the present invention discloses isolated and purified engineeredclumping factor A protein (ClfA) with a stabilized, closed conformation and immunogenic compositions thereof including methods of treating ainfection in an individual.

Crystal structure ofclumping factor A in complex with fibrinogen derived peptide and uses thereof

The present invention provides a method for determining the structure of a microbial surface components recognizing adhesive matrix molecule in complex with fibrinogen, by providing a ClfA complexed with a fibrinogen gamma-peptide; determining a ClfA binding region of the fibrinogen gamma-peptide; determining one or more critical amino acid residues in the ClfA binding region of a native fibrinogen gamma-peptide that is critical for a ClfA:fibrinogen gamma-peptide interaction; determining one or more amino acid residues of the ClfA that binds to the ClfA binding region of the native fibrinogen gamma-peptide; modeling the structure of the ClfA binding region; determining the structure of the ClfA in complex with the :fibrinogen gamma-peptide interaction; and identifying one or more potential agent(s) that inhibit the ClfA:fibrinogen gamma-peptide interaction without affecting binding of other proteins to the fibrinogen gamma-peptide.

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Sodra Sanby, Sweden

Emanuel Smeds