Sphingomyelin phosphodiesterase
| Sphingomyelin phosphodiesterase | |||||||||
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Crystal structure of sphingomyelinase from Bacillus cereus.
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| Identifiers | |||||||||
| EC number | 3.1.4.12 | ||||||||
| CAS number | 9031-54-3 | ||||||||
| Databases | |||||||||
| IntEnz | IntEnz view | ||||||||
| BRENDA | BRENDA entry | ||||||||
| ExPASy | NiceZyme view | ||||||||
| KEGG | KEGG entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| PRIAM | profile | ||||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||||
| Gene Ontology | AmiGO / EGO | ||||||||
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| Search | |
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| PMC | articles |
| PubMed | articles |
| NCBI | proteins |
Sphingomyelin phosphodiesterase (EC 3.1.4.12, also known as neutral sphingomyelinase, sphingomyelinase, or SMase) is a hydrolase enzyme that is involved in sphingolipid metabolism reactions. SMase is a member of the DNase I superfamily of enzymes and is responsible for breaking sphingomyelin (SM) down into phosphocholine and ceramide. The activation of SMase has been suggested as a major route for the production of ceramide in response to cellular stresses.
Currently, five types of SMase have been identified. These are classified according to their cation dependence and pH optima of action and are:
Of these, the lysosomal acidic SMase and the magnesium-dependent neutral SMase are considered major candidates for the production of ceramide in the cellular response to stress.
Neutral sphingomyelinase (N-SMase) activity was first described in fibroblasts from patients with Niemann-Pick disease – a lysosomal storage disease characterized by deficiencies in acid SMase. Subsequent study found that this enzyme was the product of a distinct gene, had an optimum pH of 7.4, was dependent on Mg2+ ions for activity, and was particularly enriched in brain. However, a more recent study in bovine brain suggested the existence of multiple N-SMase isoforms with different biochemical and chromatographical properties.
A major breakthrough came in the mid-1980s with the cloning of the first N-SMases from Bacillus cereus and Staphylococcus aureus. Using the sequences of these bacterial sphingomyelinases in homology searches ultimately led to the identification of the yeast N-SMases ISC1 in the budding yeast Saccharomyces cerevisiae and the mammalian N-SMase enzymes, nSMase1 and nSMase2. The identity between mammalian, yeast and bacterial SMases is very low - being approximately 20% between nSMase2 and the B. cereus SMase. However, an alignment of the sequences (see figure) indicate a number of conserved residues throughout the family, particularly in the catalytic region of the enzymes. This has led to the suggestion of a common catalytic mechanism for the N-SMase family.
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