2QFF

Crystal structure of Staphylococcal Complement Inhibitor

Summary for 2QFF

• Entry DOI: 10.2210/pdb2qff/pdb
• Descriptor: Hypothetical protein (2 entities in total)
• Functional Keywords: complement, inhibitor, inflammation, bacterial, molecular biology, hydrolase inhibitor
• Biological source: Staphylococcus aureus subsp. aureus
• Cellular location: Secreted (By similarity): Q2FFF8
• Total number of polymer chains: 1
• Total formula weight: 9533.49

Authors

Milder, F.J.,Rooijakkers, S.H.M.,Bardoel, B.W.,Ruyken, M.,Van Strijp, J.A.G.,Gros, P. (deposition date: 2007-06-27, release date: 2007-09-04, Last modification date: 2024-10-30)

Primary citation

Rooijakkers, S.H.,Milder, F.J.,Bardoel, B.W.,Ruyken, M.,van Strijp, J.A.,Gros, P.
Staphylococcal complement inhibitor: structure and active sites.
J.Immunol., 179:2989-2998, 2007

PubMed Abstract: 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.

PubMed: 17709514

Experimental method

X-RAY DIFFRACTION (1.8 Å)