This Sandbox is Reserved from January 10, 2010, through April 10, 2011 for use in BCMB 307-Proteins course taught by Andrea Gorrell at the University of Northern British Columbia, Prince George, BC, Canada.

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2dds, resolution 1.80Å ()

Ligands:

Activity:

Sphingomyelin phosphodiesterase, with EC number 3.1.4.12

Related:

2ddr, 2ddt

Structural annotation:
Resources:	InterPro : Ipr005135 Pfam : PF03372 UniProt : P11889

Functional annotation:
Biological process:	cytolysis hemolysis by symbiont of host red blood cells
Molecular function:	sphingomyelin phosphodiesterase activity hydrolase activity

Evolutionary conservation:

Toggle Conservation Colors:	Rows = identical sequences:
Further Information:	Caveats, Explanation, Complete Results at ConSurfDB

Resources:

FirstGlance, OCA, PDBsum, RCSB, TOPSAN

Coordinates:

save as pdb, mmCIF, xml

IntroductionIntroduction

Sphingomyelin phosphodiesterase (Sphingomyelinase): (SMase) is an enzyme which catalyzes the hydrolysis of sphingomyelin to ceramide and phosphocholine ^[1]. This enzyme has become the object of renewed interest since the discovery of the sphingomyelin signal transduction pathway which is involved in apoptosis. This pathway is initiated by a neutral sphingomyelinase hydrolysis of sphingomyelin in the plasma membrane to generate ceramide. Ceramide acts as a secondary messenger which causes the stimulation of the cascade effect of kinases and transcription factors which activate programmed cell death^[2]. There are 6 known types of sphingomyelinases^[3]. :

Acid sphingomyelinase (aSMase) -

Secretory sphingomyelinase (sSMase) -

Neutral Mg2+-dependent sphingomyelinases (nSMase) -

Neutral Mg2+-independent sphingomyelinases -

Alkaline sphingomyelinase -

Bacterial sphingomyelinase -

Structure and FunctionStructure and Function

Recently, in the 1980's, the primary structure of sphingomyelinase was determined by cloning the first N-SMases from Bacillus cereus and Staphylococcus aureus and by the subsequent sequencing of their cDNAs ^[4]. The crystal structure of sphingomyelinase has been solved using Listeria ivanovii and Bacillus cereus(Bc-SMase) to gain further insight into its catalytic activities ^[5].

MechanismMechanism

The mechanism of shingomyelinase catalytic activity is not fully understood in atomic detail because the cystal structures of SMase in complex with the essential divalent metal ions, Co2+, Mn2+, Mg2+, Ca2+, and Sr2+, has not been clarified ^[5].

Importance of SMaseImportance of SMase

ReferencesReferences

↑ Ago H, Oda M, Takahashi M, Tsuge H, Ochi S, Katunuma N, Miyano M, Sakurai J. Structural basis of the sphingomyelin phosphodiesterase activity in neutral sphingomyelinase from Bacillus cereus. J Biol Chem. 2006 Jun 9;281(23):16157-67. Epub 2006 Apr 4. PMID:16595670 doi:10.1074/jbc.M601089200
↑ Kolesnick RN, Haimovitz-Friedman A, Fuks Z. The sphingomyelin signal transduction pathway mediates apoptosis for tumor necrosis factor, Fas, and ionizing radiation. Biochem Cell Biol. 1994 Nov-Dec;72(11-12):471-4. PMID:7544586
↑ Goni FM, Alonso A. Sphingomyelinases: enzymology and membrane activity. FEBS Lett. 2002 Oct 30;531(1):38-46. PMID:12401200
↑ Tomita M, Nakai K, Yamada A, Taguchi R, Ikezawa H. Secondary structure of sphingomyelinase from Bacillus cereus. J Biochem. 1990 Nov;108(5):811-5. PMID:2127932
↑ ^5.0 ^5.1 Ago H, Oda M, Takahashi M, Tsuge H, Ochi S, Katunuma N, Miyano M, Sakurai J. Structural basis of the sphingomyelin phosphodiesterase activity in neutral sphingomyelinase from Bacillus cereus. J Biol Chem. 2006 Jun 9;281(23):16157-67. Epub 2006 Apr 4. PMID:16595670 doi:10.1074/jbc.M601089200

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA, Justine Doherty

[gp-1] Ago H, Oda M, Takahashi M, Tsuge H, Ochi S, Katunuma N, Miyano M, Sakurai J. Structural basis of the sphingomyelin phosphodiesterase activity in neutral sphingomyelinase from Bacillus cereus. J Biol Chem. 2006 Jun 9;281(23):16157-67. Epub 2006 Apr 4. PMID:16595670 doi:10.1074/jbc.M601089200

[gp2-2] Kolesnick RN, Haimovitz-Friedman A, Fuks Z. The sphingomyelin signal transduction pathway mediates apoptosis for tumor necrosis factor, Fas, and ionizing radiation. Biochem Cell Biol. 1994 Nov-Dec;72(11-12):471-4. PMID:7544586

[gp3-3] Goni FM, Alonso A. Sphingomyelinases: enzymology and membrane activity. FEBS Lett. 2002 Oct 30;531(1):38-46. PMID:12401200

[gp4-4] Tomita M, Nakai K, Yamada A, Taguchi R, Ikezawa H. Secondary structure of sphingomyelinase from Bacillus cereus. J Biochem. 1990 Nov;108(5):811-5. PMID:2127932

[gp5-5] 5.0 ^5.1 Ago H, Oda M, Takahashi M, Tsuge H, Ochi S, Katunuma N, Miyano M, Sakurai J. Structural basis of the sphingomyelin phosphodiesterase activity in neutral sphingomyelinase from Bacillus cereus. J Biol Chem. 2006 Jun 9;281(23):16157-67. Epub 2006 Apr 4. PMID:16595670 doi:10.1074/jbc.M601089200

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