Identification of new sphingomyelinases D in pathogenic fungi and other pathogenic organisms

• Published in: PloS one 2013-11, Vol.8 (11), p.e79240-e79240
• Main Authors: Dias-Lopes, Camila, Neshich, Izabella A P, Neshich, Goran, Ortega, José Miguel, Granier, Claude, Chávez-Olortegui, Carlos, Molina, Franck, Felicori, Liza
• Format: Article
• Language: English
• Subjects: Acids; Amino Acid Motifs - genetics; Amino Acid Sequence; Amino acids; Animals; Arthropod Proteins - chemistry; Arthropod Proteins - genetics; Arthropod Proteins - metabolism; Aspergillus flavus; Aspergillus flavus - enzymology; Aspergillus flavus - genetics; Bacterial Proteins - chemistry; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Biocatalysis; Bioinformatics; Bites; Catalytic Domain; Corynebacterium pseudotuberculosis; Corynebacterium pseudotuberculosis - classification; Corynebacterium pseudotuberculosis - enzymology; Corynebacterium pseudotuberculosis - genetics; Enzymes; Fungal Proteins - chemistry; Fungal Proteins - genetics; Fungal Proteins - metabolism; Fungi; Fungi - classification; Fungi - enzymology; Fungi - genetics; Genetic aspects; Insect bites; Ixodes - classification; Ixodes - enzymology; Ixodes - genetics; Microorganisms; Models, Molecular; Molecular Sequence Data; Organisms; Phosphodiesterases; Phosphoric Diester Hydrolases - chemistry; Phosphoric Diester Hydrolases - genetics; Phosphoric Diester Hydrolases - metabolism; Phylogenetics; Phylogeny; Protein Structure, Secondary; Protein Structure, Tertiary; Proteins; Renal failure; Sequence Homology, Amino Acid; Skin; Sphingomyelins - chemistry; Sphingomyelins - metabolism; Spiders; Spiders - classification; Spiders - enzymology; Spiders - genetics; Toxins
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0079240

Sphingomyelinases D (SMases D) or dermonecrotic toxins are well characterized in Loxosceles spider venoms and have been described in some strains of pathogenic microorganisms, such as Corynebacterium sp. After spider bites, the SMase D molecules cause skin necrosis and occasional severe systemic manifestations, such as acute renal failure. In this paper, we identified new SMase D amino acid sequences from various organisms belonging to 24 distinct genera, of which, 19 are new. These SMases D share a conserved active site and a C-terminal motif. We suggest that the C-terminal tail is responsible for stabilizing the entire internal structure of the SMase D Tim barrel and that it can be considered an SMase D hallmark in combination with the amino acid residues from the active site. Most of these enzyme sequences were discovered from fungi and the SMase D activity was experimentally confirmed in the fungus Aspergillus flavus. Because most of these novel SMases D are from organisms that are endowed with pathogenic properties similar to those evoked by these enzymes alone, they might be associated with their pathogenic mechanisms.