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Overview for MACiE Entry M0242

Version history

General Information

EC Number: 3.1.4.41 (A member of the Hydrolases, Acting on ester bonds, Phosphoric-diester hydrolases)

Enzyme Name: sphingomyelin phosphodiesterase D

Biological Species: Loxosceles laeta (South american recluse spider)

Catalytic Chain UniprotKB Accession Codes:

  • Q8I914 - Sphingomyelin phosphodiesterase D LlSicTox-alphaIII1i

Representative PDB Code: 2f9r - CRYSTAL STRUCTURE OF THE INACTIVE STATE OF THE SMASE I, ASPHINGOMYELINASE D FROM LOXOSCELES LAETA VENOM (Resolution = 1.85 Å).

Catalytic CATH Codes:

  • 3.20.20.190 - Phosphatidylinositol (PI) phosphodiesterase

Display structure information

Overall Reaction:

Image of water

Image of Sphingomyelin

right arrow

Image of Ceramide 1-phosphate

Image of Choline

water
C00001
CHEBI:15377
Sphingomyelin
C00550
CHEBI:58216
Ceramide 1-phosphate
C02960
Choline
C00114
CHEBI:15354

Overall Comment: In addition to hydrolysing sphingomyelin, the enzyme can hydrolyse lysophosphatidyl choline to lysophosphatidic acid and choline.


View similar reactions


Stepwise Description of the Reaction

Step 1His47 is the nucleophile for attack on the phosphorous of the scissile phosphodiester. A penta-coordinated intermediate is formed.
Step 2The intermediate collapses and eliminates choline, which is protonated by His12.
Step 3His12 deprotonates water, which then acts as the nucleophile for attack on the phosphorous centre of the intermediate. A penta-coordinated intermediate is formed.
Step 4The intermediate collapses and eliminates His47. This forms ceramide 1-phosphate.

View similar reactions (composite manual annotation)


Catalytic Residues Involved

Type Number Chain Location of Function
His 47 A Side Chain
His 12 A Side Chain
Gly 48 A Main Chain Carbonyl
Asp 34 A Side Chain
Asn 252 A Side Chain
Asp 233 A Side Chain
Asp 52 A Side Chain
Trp 230 A Side Chain
Lys 93 A Side Chain

Metal Cofactors for M0242

Type Het group Number Chain
magnesium MG 601 _ Overview

References

  1. M. T. Murakami et al. (2005), J. Biol. Chem., 280, 13658-13664. Structural basis for metal ion coordination and the catalytic mechanism of sphingomyelinases D.
    Medline: 15654080
  2. H. Ago et al. (2006), J. Biol. Chem., 281, 16157-16167. Structural basis of the sphingomyelin phosphodiesterase activity in neutral sphingomyelinase from Bacillus cereus.
    Medline: 16595670
  3. T. Obama et al. (2003), Biol. Pharm. Bull., 26, 920-926. His151 and His296 are the acid-base catalytic residues of Bacillus cereus sphingomyelinase in sphingomyelin hydrolysis.
    Medline: 12843611
  4. M. T. Murakami et al. (2006), Biochem. Biophys. Res. Commun., 342, 323-329. Structural insights into the catalytic mechanism of sphingomyelinases D and evolutionary relationship to glycerophosphodiester phosphodiesterases.
    Medline: 16480957

Homologue information for M0242 (2f9r)

CSA Homologues

MACiE Homologues (within the PDB)

MACiE Homologues (within UniprotKB/SwissProt)



Entries with at least one Catalytic CATH code in common (different mechanisms):

MACiE Entry Enzyme Name
EC Number
PDB code CATH code Composite
Reaction Similarity
Catalytic Machinery
Similarity
M0028 phosphoinositide phospholipase C
3.1.4.11
1djx 3.20.20.190
0.35480.2499Compare
M0300 glycerophosphodiester phosphodiesterase
3.1.4.46
2pz0 3.20.20.190
0.47820.488Compare
M0026 phosphatidylinositol diacylglycerol-lyase
4.6.1.13
1ptd 3.20.20.190
0.42850.5625Compare

View a comparison of the other reactions in MACiE with the CATH domain 3.20.20.190


Links to this entry in other databases

Link to EC-PDB-SUM Link to PDB-SUM Link to RCSB PDB Link to PDBe Link to CSA
Link to MetaCyc Link to KEGG Link to BRENDA Link to ExplorENZ

GOA logo
extracellular region (cellular component)
lipid metabolic process (biological process)
phosphoric diester hydrolase activity (molecular function)
hydrolase activity (molecular function)
cytolysis (biological process)
hemolysis in other organism (biological process)
metal ion binding (molecular function)
sphingomyelin phosphodiesterase D activity (molecular function)
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