NarE: a novel ADP-ribosyltransferase from Neisseria meningitidis.
Mono ADP-ribosyltransferases (ADPRTs) are a class of functionally conserved enzymes present in prokaryotic and eukaryotic organisms. In bacteria, these enzymes often act as potent toxins and play an important role in pathogenesis. Here we report a profile-based computational approach that, assisted by secondary structure predictions, has allowed the identification of a previously undiscovered ADP-ribosyltransferase in Neisseria meningitidis (NarE). NarE shows structural homologies with E. coli heat-labile enterotoxin (LT) and cholera toxin (CT) and possesses ADP-ribosylating and NAD-glycohydrolase activities. As in the case of LT and CT, NarE catalyses the transfer of the ADP-ribose moiety to arginine residues. Despite the absence of a signal peptide, the protein is efficiently exported into the periplasm of Neisseria. The narE gene is present in 25 out of 43 strains analysed, is always present in ET-5 and Lineage 3 but absent in ET-37 and Cluster A4 hypervirulent lineages. When present, the gene is 100% conserved in sequence and is inserted upstream of and co-transcribed with the lipoamide dehydrogenase E3 gene. Possible roles in the pathogenesis of N. meningitidis are discussed.
Masignani
Vega
V
IRIS, Chiron s.r.l, via Fiorentina 1, 53100 Siena, Italy.
Balducci
Enrico
E
Di Marcello
Federica
F
Savino
Silvana
S
Serruto
Davide
D
Veggi
Daniele
D
Bambini
Stefania
S
Scarselli
Maria
M
Aricò
Beatrice
B
Comanducci
Maurizio
M
Adu-Bobie
Jeannette
J
Giuliani
Marzia M
MM
Rappuoli
Rino
R
Pizza
Mariagrazia
M
D036002:ADP Ribose Transferases / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000378:metabolism; D001427:Bacterial Toxins / Q000378:metabolism; D001483:Base Sequence; D002772:Cholera Toxin / Q000378:metabolism; D004229:Dithiothreitol / Q000494:pharmacology; D004768:Enterotoxins / Q000378:metabolism; D029968:Escherichia coli Proteins; D008274:Magnesium / Q000494:pharmacology; D008969:Molecular Sequence Data; D005810:Multigene Family; D009243:NAD / Q000378:metabolism; D009244:NAD+ Nucleosidase / Q000378:metabolism; D038541:Neisseria meningitidis, Serogroup B / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity; D019897:Periplasm / Q000378:metabolism; D021382:Protein Sorting Signals; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D014774:Virulence / Q000235:genetics
D000596:Amino Acids; D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D021382:Protein Sorting Signals; D009243:NAD; D002772:Cholera Toxin; C027538:heat-labile enterotoxin, E coli; D036002:ADP Ribose Transferases; C480854:NarE protein, Neisseria meningitidis; D009244:NAD+ Nucleosidase; D008274:Magnesium; D004229:Dithiothreitol