Ceramidase: Difference between revisions
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Upon ligand binding, CerN enters the <scene name='91/910024/Closedsurf_use/1'>closed</scene> conformation. <ref name="Inoue">PMID:19088069</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.<ref name="Inoue">PMID:19088069</ref> 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="Inoue">PMID:19088069</ref> | Upon ligand binding, CerN enters the <scene name='91/910024/Closedsurf_use/1'>closed</scene> conformation. <ref name="Inoue">PMID:19088069</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.<ref name="Inoue">PMID:19088069</ref> 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="Inoue">PMID:19088069</ref> | ||
[[Image:CerN Mechanism Okino2009.jpg|300px| | [[Image:CerN Mechanism Okino2009.jpg|300px|right|thumb|'''Figure 1''' Proposed mechanism of the zinc-dependent hydrolysis of C2-ceramide by CerN. Figure adapted from Inoe et al.(2009)<ref name="Inoue">PMID:19088069</ref>]] | ||
Refs <ref name="Okino">PMID:9603946</ref>, <ref name="Inoue">PMID:19088069</ref> , <ref name="Reverse">PMID:10832092</ref> | Refs <ref name="Okino">PMID:9603946</ref>, <ref name="Inoue">PMID:19088069</ref> , <ref name="Reverse">PMID:10832092</ref> | ||
