Ceramidase: Difference between revisions

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== Function ==

~~'''CerN'''~~ is an enzyme that catalyzes the cleavage of the [https://en.wikipedia.org/wiki/Sphingolipid Sphingolipid] <scene name='91/910024/Ceramide/3'>Ceramide</scene> at the <scene name='91/910024/Ceramide18/1'>N-acyl linkage</scene>, producing <scene name='91/910024/Ceramide/4'>sphingosine and a fatty acid</scene>.<ref name="Okino">PMID:9603946</ref> <ref name="Inoue">PMID:19088069</ref>

‘’’CerN’’’ is an enzyme that catalyzes the cleavage of the [https://en.wikipedia.org/wiki/Sphingolipid Sphingolipid] <scene name='91/910024/Ceramide/3'>Ceramide</scene> at the <scene name='91/910024/Ceramide18/1'>N-acyl linkage</scene>, producing <scene name='91/910024/Ceramide/4'>sphingosine and a fatty acid</scene>.<ref name="Okino">PMID:9603946</ref> <ref name="Inoue">PMID:19088069</ref> CerN cleaves the N-acyl linkage within ceramides via ‘’’zinc-dependent hydrolysis’’’ and the enzyme is also capable of synthesizing ceramide from sphingosine and palmitic acid by the reverse mechanism. <ref name="Reverse">PMID:10832092</ref> <ref name="Okino">PMID:9603946</ref> The zinc ion within the <scene name='91/910024/Activesite2/3'>active site</scene> is coordinated by His97, His204, Glu411, Tyr448, and a water molecule. His97 and Tyr448 are required for zinc binding within the active site. ‘’Ligand binding within the active site is recognized by Gly25, His99, Arg160, and Tyr460’’. <ref name="Okino">PMID:9603946</ref> Ser27 and Gly25 stabilize ceramide within the active site by forming a water-mediated hydrogen bond with the central OH of ceramide, and the carbonyl oxygen is stabilized by the Tyr448 and Tyr460.

Upon ligand binding, CerN enters the <scene name='91/910024/Closedsurf_use/1'>closed</scene> conformation. <ref name="Okino">PMID:9603946</ref> ‘’’His99’’’ and ‘’’Arg160’’’ function in the ‘’’catalysis of ceramide hydrolysis’’’, as they deprotonate their coordinated water molecule to produce a hydroxide ion. The carbonyl carbon of ceramide undergoes a ‘’nucleophilic attack’’ by the hydroxide ion. The carbonyl oxygen stabilized by Tyr448 and Tyr460 is then passed to the zinc ion, allowing for the breakage of the N-acyl linkage. Sphingosine is then released from the active site while the fatty acid remains bound to the zinc ion until it is replaced by a new water molecule, shifting CerN into the

<scene name='91/910024/Activesite_open_surf/2'>open</scene>conformation. The synthesis of ceramide from palmitate and sphingosine occurs via the same mechanism, but in reverse. <ref name="Okino">PMID:9603946</ref>

Refs <ref name="Okino">PMID:9603946</ref>, <ref name="Inoue">PMID:19088069</ref> , <ref name="Reverse">PMID:10832092</ref>

Ceramidase: Difference between revisions

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 <StructureSection load='2zxc' size='340' side='right' caption="CerN bound to C2 Ceramide [[2zxc]]", [[Resolution|resolution]] 2.20&Aring;' scene='91/910024/2zxc_ballstick/2'>
 == Function ==
-'''CerN''' is an enzyme that catalyzes the cleavage of the [https://en.wikipedia.org/wiki/Sphingolipid Sphingolipid] <scene name='91/910024/Ceramide/3'>Ceramide</scene> at the <scene name='91/910024/Ceramide18/1'>N-acyl linkage</scene>, producing <scene name='91/910024/Ceramide/4'>sphingosine and a fatty acid</scene>.<ref name="Okino">PMID:9603946</ref> <ref name="Inoue">PMID:19088069</ref>
+‘’’CerN’’’ is an enzyme that catalyzes the cleavage of the [https://en.wikipedia.org/wiki/Sphingolipid Sphingolipid] <scene name='91/910024/Ceramide/3'>Ceramide</scene> at the <scene name='91/910024/Ceramide18/1'>N-acyl linkage</scene>, producing <scene name='91/910024/Ceramide/4'>sphingosine and a fatty acid</scene>.<ref name="Okino">PMID:9603946</ref> <ref name="Inoue">PMID:19088069</ref> CerN cleaves the N-acyl linkage within ceramides via ‘’’zinc-dependent hydrolysis’’’ and the enzyme is also capable of synthesizing ceramide from sphingosine and palmitic acid by the reverse mechanism. <ref name="Reverse">PMID:10832092</ref> <ref name="Okino">PMID:9603946</ref> The zinc ion within the <scene name='91/910024/Activesite2/3'>active site</scene> is coordinated by His97, His204, Glu411, Tyr448, and a water molecule. His97 and Tyr448 are required for zinc binding within the active site. ‘’Ligand binding within the active site is recognized by Gly25, His99, Arg160, and Tyr460’’. <ref name="Okino">PMID:9603946</ref> Ser27 and Gly25 stabilize ceramide within the active site by forming a water-mediated hydrogen bond with the central OH of ceramide, and the carbonyl oxygen is stabilized by the Tyr448 and Tyr460.
+Upon ligand binding, CerN enters the <scene name='91/910024/Closedsurf_use/1'>closed</scene> conformation. <ref name="Okino">PMID:9603946</ref> ‘’’His99’’’ and ‘’’Arg160’’’ function in the ‘’’catalysis of ceramide hydrolysis’’’, as they deprotonate their coordinated water molecule to produce a hydroxide ion. The carbonyl carbon of ceramide undergoes a ‘’nucleophilic attack’’ by the hydroxide ion. The carbonyl oxygen stabilized by Tyr448 and Tyr460 is then passed to the zinc ion, allowing for the breakage of the N-acyl linkage. Sphingosine is then released from the active site while the fatty acid remains bound to the zinc ion until it is replaced by a new water molecule, shifting CerN into the
+<scene name='91/910024/Activesite_open_surf/2'>open</scene>conformation. The synthesis of ceramide from palmitate and sphingosine occurs via the same mechanism, but in reverse. <ref name="Okino">PMID:9603946</ref>
 Refs <ref name="Okino">PMID:9603946</ref>, <ref name="Inoue">PMID:19088069</ref> , <ref name="Reverse">PMID:10832092</ref>