5UZU

Immune evasion by a Staphylococcal Peroxidase Inhibitor that blocks myeloperoxidase

Summary for 5UZU

• Entry DOI: 10.2210/pdb5uzu/pdb
• Descriptor: Uncharacterised protein, Myeloperoxidase, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (8 entities in total)
• Functional Keywords: myeloperoxidase, phagolysosome, staphylococcal inhibitor innate immunity, oxidoreductase
• Biological source: Staphylococcus aureus; More
• Total number of polymer chains: 2
• Total formula weight: 75269.80

Authors

de Jong, N.,Geisbrecht, B.V.,van Strijp, J.,Haas, P.,Nijland, R.,Ramyar, K.,Fevre, C.,Guerra, F.,Voyich-Kane, J.,van Kessel, C.,Garcia, B. (deposition date: 2017-02-27, release date: 2017-07-26, Last modification date: 2024-11-06)

Primary citation

de Jong, N.W.M.,Ramyar, K.X.,Guerra, F.E.,Nijland, R.,Fevre, C.,Voyich, J.M.,McCarthy, A.J.,Garcia, B.L.,van Kessel, K.P.M.,van Strijp, J.A.G.,Geisbrecht, B.V.,Haas, P.A.
Immune evasion by a staphylococcal inhibitor of myeloperoxidase.
Proc. Natl. Acad. Sci. U.S.A., 114:9439-9444, 2017

PubMed Abstract: is highly adapted to its host and has evolved many strategies to resist opsonization and phagocytosis. Even after uptake by neutrophils, shows resistance to killing, which suggests the presence of phagosomal immune evasion molecules. With the aid of secretome phage display, we identified a highly conserved protein that specifically binds and inhibits human myeloperoxidase (MPO), a major player in the oxidative defense of neutrophils. We have named this protein "staphylococcal peroxidase inhibitor" (SPIN). To gain insight into inhibition of MPO by SPIN, we solved the cocrystal structure of SPIN bound to a recombinant form of human MPO at 2.4-Å resolution. This structure reveals that SPIN acts as a molecular plug that prevents HO substrate access to the MPO active site. In subsequent experiments, we observed that SPIN expression increases inside the neutrophil phagosome, where MPO is located, compared with outside the neutrophil. Moreover, bacteria with a deleted gene encoding SPIN showed decreased survival compared with WT bacteria after phagocytosis by neutrophils. Taken together, our results demonstrate that secretes a unique proteinaceous MPO inhibitor to enhance survival by interfering with MPO-mediated killing.

PubMed: 28808028
DOI: 10.1073/pnas.1707032114

Experimental method

X-RAY DIFFRACTION (2.403 Å)