Sandbox Reserved 313: Difference between revisions
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''Secretory sphingomyelinase (sSMase)'' - | ''Secretory sphingomyelinase (sSMase)'' - | ||
''Neutral Mg2+-dependent sphingomyelinases (nSMase)'' - | ''Neutral Mg2+-dependent sphingomyelinases (nSMase)'' - The membrane bound dependent nSMase has an neatral pH optimum and is found predominantly in the brain. This neutral SMase enzyme relies on Magnesium and is activated by unsaturated fatty acids and phosphatidylserine<ref name="gp6">PMID: 10713073 </ref>. | ||
''Neutral Mg2+-independent sphingomyelinases'' - | ''Neutral Mg2+-independent sphingomyelinases'' - | ||
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=Structure and Function= | =Structure 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 <ref name=" | 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 <ref name="gp7">PMID: 2127932 </ref>. | ||
The crystal structure of sphingomyelinase has been solved using the bacterium ''Listeria ivanovii'' and ''Bacillus cereus(Bc-SMase)'' to gain further insight into its catalytic activities <ref name=" | The crystal structure of sphingomyelinase has been solved using the bacterium ''Listeria ivanovii'' and ''Bacillus cereus(Bc-SMase)'' to gain further insight into its catalytic activities <ref name="gp6">PMID: 16595670 </ref>. The overall structure of Bc-SMase has been determined to consist of a β-sandwich with α/β motifs<ref name="gp">PMID: 16595670 </ref>. Through SMase structure identification, it has been determined to be a member of the DNA I-like superfamily having geometrically identical amino acid residues as the enzymes in this superfamily. The only different with SMase, is that it has a unique hydrophobic beta-hairpin structure. The crystal structure revealed that this unique beta-hairpin region has two solvent exposed aromatic amino acids on the top which bind to the cell surfaces to catalyze hemolysis. | ||
=Mechanism= | =Mechanism= | ||
It has been proposed that the mechanism of Bc-SMase is similar to that of bovine pancreatic DNase 1 because Bc-SMase and bovine DNase 1 are homologous proteins which both have conserved alleged catalytic amino acid residues and a similar molecular structure<ref name=" | It has been proposed that the mechanism of Bc-SMase is similar to that of bovine pancreatic DNase 1 because Bc-SMase and bovine DNase 1 are homologous proteins which both have conserved alleged catalytic amino acid residues and a similar molecular structure<ref name="gp7">PMID: 16595670 </ref>. . The proposed hydrolytic activity of Bc-SMAse cloned from ''Bacillus cereus'' is coordinated by essential water bridged divalent metal ions. Two metal ions which are bound to the Glu-53 and <scene name='Sandbox_Reserved_313/His-296/2'>His-296</scene> residues in the central cleft which orientate the substrate in the active site. The divalent cation which is linked to His-296 provides a general base water and a phosphate from sphingomelin binds to the central cleft at the site of the water bridged double metal ions. The divalent metal ion which is located at Glu-53 then binds to sphingomelin by directly interacting with the amide oxygen and the O-4 ester oxygen. | ||
=Implications= | =Implications= | ||
The crystal structure of Bc-SMase has some significant implications for unlocking the poorly characterized structure of neutral sphingomyelinase (nSMase) found in mammals. Bc-SMase is a homologue of nSMase, sharing similar metal ion dependence, amino acid sequence identity, and a similar hydrolytic mechanism<ref name="gp">PMID: 16595670 </ref>. | The crystal structure of Bc-SMase has some significant implications for unlocking the poorly characterized structure of neutral sphingomyelinase (nSMase) found in mammals. Bc-SMase is a homologue of nSMase, sharing similar metal ion dependence, amino acid sequence identity, and a similar hydrolytic mechanism<ref name="gp">PMID: 16595670 </ref>. | ||
=References= | =References= | ||
<references/> | <references/> | ||