title: A non-catalytic histidine residue influences the function of the metalloprotease of Listeria monocytogenes.
abstract: Mpl, a thermolysin-like metalloprotease, and PC-PLC, a phospholipase C, are synthesized as proenzymes by the intracellular bacterial pathogen Listeria monocytogenes. During intracellular growth, L. monocytogenes is temporarily confined in a membrane-bound vacuole whose acidification leads to Mpl autolysis and Mpl-mediated cleavage of the PC-PLC N-terminal propeptide. Mpl maturation also leads to the secretion of both Mpl and PC-PLC across the bacterial cell wall. Previously, we identified negatively charged and uncharged amino acid residues within the N terminus of the PC-PLC propeptide that influence the ability of Mpl to mediate the maturation of PC-PLC, suggesting that these residues promote the interaction of the PC-PLC propeptide with Mpl. In the present study, we identified a non-catalytic histidine residue (H226) that influences Mpl secretion across the cell wall and its ability to process PC-PLC. Our results suggest that a positive charge at position 226 is required for Mpl functions other than autolysis. Based on the charge requirement at this position, we hypothesize that this residue contributes to the interaction of Mpl with the PC-PLC propeptide.
authors.affiliation: Department of Microbiology and Immunology, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Brian M
authors.initials: BM
authors.lastname: Forster
authors.affiliation: Department of Microbiology and Immunology, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Alan Pavinski
authors.initials: AP
authors.lastname: Bitar
authors.affiliation: Department of Microbiology and Immunology, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Hélène
authors.initials: H
authors.lastname: Marquis
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism*; D004792:Enzyme Precursors / Q000378:metabolism; D006639:Histidine / Q000235:genetics* / Q000378:metabolism*; D008089:Listeria monocytogenes / Q000201:enzymology* / Q000235:genetics*; D008666:Metalloendopeptidases / Q000235:genetics* / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D004792:Enzyme Precursors; D006639:Histidine; D010738:Type C Phospholipases; C105598:phosphatidylcholine-specific phospholipase C; D008666:Metalloendopeptidases; C080367:mpl protein, Listeria monocytogenes