<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="6.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Haspel, N.</style></author><author><style face="normal" font="default" size="100%">Ricklin, D.</style></author><author><style face="normal" font="default" size="100%">Geisbrecht, B.</style></author><author><style face="normal" font="default" size="100%">Lambris, J.D.</style></author><author><style face="normal" font="default" size="100%">L. E. Kavraki</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Electrostatic Contributions Drive the Interaction Between Staphylococcus aureus Protein Efb-C and its Complement Target C3d.</style></title><secondary-title><style face="normal" font="default" size="100%">Protein Science</style></secondary-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Hydrodynamics; Complement; Efb-C; Electrostatics; Protein-protein Interaction</style></keyword><keyword><style  face="normal" font="default" size="100%">kavrakilab</style></keyword><keyword><style  face="normal" font="default" size="100%">Proteins of the Immune System; Structure; Computational Analysis of Protein Structure; Molecular mechanics/dynamics; Thermodynamics</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2008</style></year><pub-dates><date><style  face="normal" font="default" size="100%">11/2008</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">17(11)</style></volume><pages><style face="normal" font="default" size="100%">1894-1906</style></pages><abstract><style face="normal" font="default" size="100%">The C3-inhibitory domain of Staphylococcus aureus extracellular fibrinogen-binding protein (Efb-C) defines a novel three-helix bundle motif that regulates complement activation. Previous crystallographic studies of Efb-C bound to its cognate sub-domain of human C3 (C3d) identified Arg-131 and Asn-138 of Efb-C as key residues for its activity. In order to characterize more completely the physical and chemical driving forces behind this important interaction, we employed in this study a combination of structural, biophysical, and computational methods to analyze the interaction of C3d with Efb-C and the single point mutants R131A and N138A. Our results show that while these mutations do not drastically affect the structure of the Efb-C/C3d recognition complex, they have significant adverse effects on both the thermodynamic kinetic profiles of the resulting complexes. We also characterized other key interactions along the Efb-C/C3d binding interface and found an intricate network of salt bridges and hydrogen bonds that anchor Efb-C to C3d, resulting in its potent complement inhibitory properties.</style></abstract></record></records></xml>
