2qff
Crystal structure of Staphylococcal Complement Inhibitor
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OverviewOverview
The pathogenic bacterium Staphylococcus aureus counteracts the host immune, defense by excretion of the 85 residue staphylococcal complement inhibitor, (SCIN). SCIN inhibits the central complement convertases; thereby, it, reduces phagocytosis following opsonization and efficiently blocks all, downstream effector functions. In this study, we present the crystal, structure of SCIN at 1.8 A resolution and the identification of its active, site. Functional characterization of structure based chimeric proteins, consisting of SCIN and the structurally but nonfunctional homologue open, reading frame-D, indicate an 18-residue segment (Leu-31-Gly-48) crucial, for SCIN activity. In all complement activation pathways, chimeras lacking, these SCIN residues completely fail to inhibit production of the potent, mediator of inflammation C5a. Inhibition of alternative pathway-mediated, opsonization (C3b deposition) and formation of the lytic membrane attack, complex (C5b-9 deposition) are strongly reduced for these chimeras as, well. For inhibition of the classical/lectin pathway-mediated C3b and, C5b-9 deposition, the same residues are critical although additional sites, are involved. These chimeras also display reduced capacity to stabilize, the C3 convertases of both the alternative and the classical/lectin, pathway indicating the stabilizing effect is pivotal for the complement, inhibitory activity of SCIN. Because SCIN specifically and efficiently, inhibits complement, it has a high potential in anti-inflammatory therapy., Our data are a first step toward the development of a second generation, molecule suitable for such therapeutic complement intervention.
About this StructureAbout this Structure
2QFF is a Single protein structure of sequence from Staphylococcus aureus. Full crystallographic information is available from OCA.
ReferenceReference
Staphylococcal complement inhibitor: structure and active sites., Rooijakkers SH, Milder FJ, Bardoel BW, Ruyken M, van Strijp JA, Gros P, J Immunol. 2007 Sep 1;179(5):2989-98. PMID:17709514
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