5fi9: Difference between revisions
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==Closed form of murine Acid Sphingomyelinase in complex with bisphosphonate inhibitor AbPA== | ==Closed form of murine Acid Sphingomyelinase in complex with bisphosphonate inhibitor AbPA== | ||
<StructureSection load='5fi9' size='340' side='right' caption='[[5fi9]], [[Resolution|resolution]] 2.54Å' scene=''> | <StructureSection load='5fi9' size='340' side='right'caption='[[5fi9]], [[Resolution|resolution]] 2.54Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5fi9]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FI9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5FI9 FirstGlance]. <br> | <table><tr><td colspan='2'>[[5fi9]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FI9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5FI9 FirstGlance]. <br> | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | |||
[[Category: Lk3 transgenic mice]] | [[Category: Lk3 transgenic mice]] | ||
[[Category: Sphingomyelin phosphodiesterase]] | [[Category: Sphingomyelin phosphodiesterase]] | ||
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[[Category: Asm]] | [[Category: Asm]] | ||
[[Category: Asmase]] | [[Category: Asmase]] | ||
[[Category: Hydrolase | [[Category: Hydrolase]] | ||
[[Category: Saposin]] | [[Category: Saposin]] | ||
[[Category: Smpd1]] | [[Category: Smpd1]] | ||
Revision as of 10:22, 23 May 2019
Closed form of murine Acid Sphingomyelinase in complex with bisphosphonate inhibitor AbPAClosed form of murine Acid Sphingomyelinase in complex with bisphosphonate inhibitor AbPA
Structural highlights
Function[ASM_MOUSE] Converts sphingomyelin to ceramide. Also has phospholipase C activities toward 1,2-diacylglycerolphosphocholine and 1,2-diacylglycerolphosphoglycerol.[UniProtKB:P17405] Publication Abstract from PubMedAcid sphingomyelinase (ASMase, ASM, SMPD1) converts sphingomyelin into ceramide, modulating membrane properties and signal transduction. Inactivating mutations in ASMase cause Niemann-Pick disease, and its inhibition is also beneficial in models of depression and cancer. To gain a better understanding of this critical therapeutic target, we determined crystal structures of mammalian ASMase in various conformations. The catalytic domain adopts a calcineurin-like fold with two zinc ions and a hydrophobic track leading to the active site. 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. Structural mapping of Niemann-Pick mutations reveals that most of them likely destabilize the protein's fold. 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. Crystal structure of mammalian acid sphingomyelinase.,Gorelik A, Illes K, Heinz LX, Superti-Furga G, Nagar B Nat Commun. 2016 Jul 20;7:12196. doi: 10.1038/ncomms12196. PMID:27435900[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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