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Structure and Function of Pneumococcal Phosphorylcholine Esterase (Pce) Provide New Insights into Pneumococcal Pathogenesis
Author(s) -
MENENDEZ Margarita,
LAGARTERA Laura,
GONZÁLEZ Ana,
GARCÍA Pedro,
GARCÍA José Luis,
HERMOSO Juan Antonio
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a902-b
Subject(s) - phosphorylcholine , lipoteichoic acid , pneumococcal pneumonia , streptococcus pneumoniae , teichoic acid , microbiology and biotechnology , phosphocholine , biology , chemistry , biochemistry , bacteria , gene , staphylococcus aureus , genetics , peptidoglycan , phospholipid , membrane , phosphatidylcholine , antibiotics
Streptococcus pneumonia causes life‐threatening diseases such as pneumonia, bacteraemia and meningitis worldwide. Many interactions of this pathogen with its host seem to be mediated by components of the bacterial cell wall. Specifically, phosphorylcholine (PC) residues of teichoic and lipoteichoic acids are recognized by components of the host response system such as the human C‐reactive protein (CRP) and the platelet‐activating factor (PAF) receptors. It also acts as a docking station for the family of modular surface‐located choline‐binding proteins (CBPs), including several virulence factors. The structure of pneumococcal phosphorylcholine esterase (PCE), a binuclear Zn 2+ metallo‐phosphoesterase belonging to the CBP family, has been solved at 1.9 Å in complex with PC (the reaction product) and choline analogues by X‐ray crystallography. Residues involved in substrate binding and catalysis are described and the modular configuration of the active site accounts for in vivo features of teichoic/lipoteichoic acid hydrolysis. The ability of Pce for hydrolyzing PAF, here reported, together with its regulatory role in phosphocholine decoration of pneumococcal surface provide new insights into the function of Pce in pneumococcal adherence and invasiveness. This work was supported by grants BIO2003‐01951, BIO2002‐02887 and BMC2003‐00074 from Dirección General de Investigación from the Spanish Ministry of Science and Technology