Plasminogen-binding activity of enolase in the opportunistic pathogen Pneumocystis carinii.
The glycolytic enzyme enolase is one of the most abundant proteins expressed in fungi and has been shown to be an immunodominant cell-wall-associated antigen of the pathogenic fungus, Candida albicans. Enolase has also been found on the surface of some mammalian cells where it functions as a plasminogen-binding motif and facilitator of plasminogen activation to plasmin. To investigate the immunogenicity of enolase in the opportunistic pathogen, Pneumocystis carinii, the genomic and complementary DNA (cDNA) enolase were cloned and characterized. The predicted protein comprises 433 amino-acid residues and shows extensive homology to other fungal enolases, including those of C. albicans (76%), Aspergillus oryzae (79%) and Saccharomyces cerevisiae (77%). The purified recombinant P. carinii enolase was immunogenic, and may be an important antigen and indicator of P. carinii infection. The active site and conformation metal ion-binding site residues necessary for dimerization and enzyme function are conserved in the predicted P. carinii enolase protein. Enolase of P. carinii is unique among the fungal enolases in that it possesses a catalytic carboxyl-terminal lysyl residue that was necessary and sufficient for the plasminogen-binding activity of the enolase of P. carinii. The activity of the plasminogen binding suggests its involvement in the local regulation of fibrinolysis within the alveolar space.
Fox
D
D
Department of Pathology, University of Cincinnati, Ohio 45267-0560, USA
Smulian
A G
AG
D000595:Amino Acid Sequence; D002473:Cell Wall / Q000378:metabolism; D003001:Cloning, Molecular; D015966:Gene Expression Regulation, Fungal; D007621:Karyotyping; D008969:Molecular Sequence Data; D010751:Phosphopyruvate Hydratase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010958:Plasminogen / Q000378:metabolism*; D011010:Pneumocystis / Q000201:enzymology*; D011994:Recombinant Proteins / Q000096:biosynthesis
D011994:Recombinant Proteins; D010958:Plasminogen; D010751:Phosphopyruvate Hydratase