Identification of new sphingomyelinases D in pathogenic fungi and other pathogenic organisms.
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.
Departamento de Bioquímica-Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
Camila
C
Dias-Lopes
Izabella A P
IA
Neshich
Goran
G
Neshich
José Miguel
JM
Ortega
Claude
C
Granier
Carlos
C
Chávez-Olortegui
Franck
F
Molina
Liza
L
Felicori
D020816:Amino Acid Motifs / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D060829:Arthropod Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001231:Aspergillus flavus / Q000201:enzymology / Q000235:genetics; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D055162:Biocatalysis; D020134:Catalytic Domain; D016925:Corynebacterium pseudotuberculosis / Q000145:classification / Q000201:enzymology* / Q000235:genetics; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D005658:Fungi / Q000145:classification / Q000201:enzymology* / Q000235:genetics; D018884:Ixodes / Q000145:classification / Q000201:enzymology* / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010727:Phosphoric Diester Hydrolases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010802:Phylogeny; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D013109:Sphingomyelins / Q000737:chemistry / Q000378:metabolism; D013112:Spiders / Q000145:classification / Q000201:enzymology* / Q000235:genetics
D060829:Arthropod Proteins; D001426:Bacterial Proteins; D005656:Fungal Proteins; D013109:Sphingomyelins; D010727:Phosphoric Diester Hydrolases; C055160:sphingomyelin phosphodiesterase D