PMID: 27435900

 

    Legend: Gene, Sites

Title : Crystal structure of mammalian acid sphingomyelinase

Abstract :

1. Acid sphingomyelinase ( ASMase , ASM , SMPD1 ) converts sphingomyelin into ceramide, modulating membrane properties and signal transduction
2. Inactivating mutations in ASMase cause Niemann-Pick disease, and its inhibition is also beneficial in models of depression and cancer
3. To gain a better understanding of this critical therapeutic target, we determined crystal structures of mammalian ASMase in various conformations
4. The catalytic domain adopts a calcineurin-like fold with two zinc ions and a hydrophobic track leading to the active site
5. Strikingly, the membrane interacting saposin domain assumes either a closed globular conformation independent from the catalytic domain , or an open conformation, which establishes an interface with the catalytic domain essential for activity
6. Structural mapping of Niemann-Pick mutations reveals that most of them likely destabilize the protein's fold
7. This study sheds light on the molecular mechanism of ASMase function, and provides a platform for the rational development of ASMase inhibitors and therapeutic use of recombinant ASMase

Output (sent_index, trigger, protein, sugar, site):

Output(Part-Of) (sent_index, protein, site):

*Output_Site_Fusion* (sent_index, protein, sugar, site):

 

Protein	NCBI ID	SENTENCE INDEX
ASMase	6609	1,2,3,7
Acid sphingomyelinase	6609	1
SMPD1	6609	1
ASM	6609	1