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| {{STRUCTURE_2qff| PDB=2qff | SCENE= }} | | {{STRUCTURE_2qff| PDB=2qff | SCENE= }} |
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- | '''Crystal structure of Staphylococcal Complement Inhibitor'''
| + | ===Crystal structure of Staphylococcal Complement Inhibitor=== |
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- | ==Overview==
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- | 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. | + | The line below this paragraph, {{ABSTRACT_PUBMED_17709514}}, adds the Publication Abstract to the page |
| + | (as it appears on PubMed at http://www.pubmed.gov), where 17709514 is the PubMed ID number. |
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| + | {{ABSTRACT_PUBMED_17709514}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Inhibitor]] | | [[Category: Inhibitor]] |
| [[Category: Molecular biology]] | | [[Category: Molecular biology]] |
- | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 14:52:07 2008'' | + | |
| + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 00:11:44 2008'' |
Revision as of 21:11, 28 July 2008
Template:STRUCTURE 2qff
Crystal structure of Staphylococcal Complement Inhibitor
Template:ABSTRACT PUBMED 17709514
About this Structure
2QFF is a Single protein structure of sequence from Staphylococcus aureus. Full crystallographic information is available from OCA.
Reference
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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