title: Insights into pneumococcal pathogenesis from the crystal structure of the modular teichoic acid phosphorylcholine esterase Pce.
abstract: Phosphorylcholine, a specific component of the pneumococcal cell wall, is crucial in pathogenesis. It directly binds to the human platelet-activating factor (PAF) receptor and acts as a docking station for the family of surface-located choline-binding proteins (CBP). The first structure of a complete pneumococcal CBP, Pce (or CbpE), has been solved in complex with the reaction product and choline analogs. Pce has a novel modular structure, with a globular N-terminal module containing a binuclear Zn(2+) catalytic center, and an elongated choline-binding module. Residues involved in substrate binding and catalysis are described and modular configuration of the active center accounts for in vivo features of teichoic acid hydrolysis. The hydrolysis of PAF by Pce and its regulatory role in phosphorylcholine decoration of the bacterial surface provide new insights into the critical function of Pce in pneumococcal adherence and invasiveness.
authors.affiliation: Grupo de Cristalografía Macromolecular y Biología Estructural, Instituto Química-Física Rocasolano, CSIC, Serrano 119, 28006 Madrid, Spain. xjuan@iqfr.csic.es
authors.forename: Juan A
authors.initials: JA
authors.lastname: Hermoso
authors.forename: Laura
authors.initials: L
authors.lastname: Lagartera
authors.forename: Ana
authors.initials: A
authors.lastname: González
authors.forename: Meike
authors.initials: M
authors.lastname: Stelter
authors.forename: Pedro
authors.initials: P
authors.lastname: García
authors.forename: Martín
authors.initials: M
authors.lastname: Martínez-Ripoll
authors.forename: José L
authors.initials: JL
authors.lastname: García
authors.forename: Margarita
authors.initials: M
authors.lastname: Menéndez
mesh_terms: D001665:Binding Sites; D002265:Carboxylic Ester Hydrolases / Q000737:chemistry*; D002794:Choline / Q000378:metabolism; D018360:Crystallography, X-Ray / Q000379:methods; D006868:Hydrolysis; D007700:Kinetics; D008958:Models, Molecular; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D013296:Streptococcus pneumoniae / Q000201:enzymology* / Q000472:pathogenicity*
chemical_list: D002265:Carboxylic Ester Hydrolases; C022718:teichoic acid phosphorylcholine esterase; D002794:Choline