Sphingomyelinase

From Proteopedia

Function Sphingomyelinase (SMase) or sphingomyelin phosphodiesterase is a hydrolase involved in sphingolipid metabolism. It catalyzes the breakdown of sphingomyelin (SM) to phosphocholine and Ceramide[1]. The SMase is classified into 5 types according to their pH dependence and cation dependence. Acid SMase-like phosphodiesterase is a paralog of acid SMase and thus though related by gene duplication has different functions. Acid SMase-like phosphodiesterase 3A hydrolyzes nucleotides triphosphates and diphosphates. Acid SMase-like phosphodiesterase 3B is a GPI-anchored protein with role in inflammatory processes and kidney disease[2]. Alkaline SMase hydrolyses sphingomyelin in the intestinal tract and bile[3]. See also Lipid signaling. Disease Mutations in acid SMase are found in patients with Niemann-Pick disease[4].

spinqualitylabelsall models Sphingomyelinase complex with glycerol and phosphate ion (PDB entry [[21zwx]) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

3D structures of sphingomyelinase

Updated on 14-August-2024

SMase

5uvg – hSMase catalytic domain – human

3rlh, 3rlg – SMase D (mutant) – Loxosceles intermedia

1xx1, 2f9r – SMase I – Loxosceles laeta

1zwx – SMase C – Listeria ivanovii

2ddr, 2dds, 2ddt – BcSMase + cation – Bacillus cereus

2uyr – BcSMase (mutant)

7cne – SMase C – Streptomyces griseocarneus

Acid SMase

5jg8, 5i81, 5i8r – hSMase

5i85 – hSMase + phosphocholine

5fib – mSMase – mouse

5hqn – mSMase catalytic domain

5fi9 – mSMase + inhibitor

5fic – mSMase + lipid

Acid SMase-like phosphodiesterase

5ebb – hSMase 3A

5ebe – hSMase 3A + CMP

5fc1, 5fc7, 5fca – mSMase 3A

5fcb – mSMase 3A + AMP

5fc6 – mSMase 3A + AMPCP

5fc5 – mSMase 3A + phosphocholine

5kar – mSMase 3B

5kas – mSMase 3B + phosphocholine

Alkaline SMase

5udy – hSMase

5tcd – hSMase + phosphocholine

References

1. ↑ Chatterjee S. Neutral sphingomyelinase: past, present and future. Chem Phys Lipids. 1999 Nov;102(1-2):79-96. PMID:11001563
2. ↑ Gorelik A, Heinz LX, Illes K, Superti-Furga G, Nagar B. Crystal Structure of the Acid Sphingomyelinase-Like Phosphodiesterase SMPDL3B Provides Insights into Determinants of Substrate Specificity. J Biol Chem. 2016 Sep 28. pii: jbc.M116.755801. PMID:27687724 doi:http://dx.doi.org/10.1074/jbc.M116.755801
3. ↑ Duan RD. Alkaline sphingomyelinase: an old enzyme with novel implications. Biochim Biophys Acta. 2006 Mar;1761(3):281-91. Epub 2006 Mar 30. PMID:16631405 doi:10.1016/j.bbalip.2006.03.007
4. ↑ Wasserstein MP, Aron A, Brodie SE, Simonaro C, Desnick RJ, McGovern MM. Acid sphingomyelinase deficiency: prevalence and characterization of an intermediate phenotype of Niemann-Pick disease. J Pediatr. 2006 Oct;149(4):554-9. PMID:17011332 doi:http://dx.doi.org/10.1016/j.jpeds.2006.06.034