Ceramidase

spinqualitylabelsall models CerN bound to C2 Ceramide 2zxc Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Function CerN is an enzyme that catalyzes the cleavage of the Sphingolipid Ceramide at the N-acyl linkage, producing sphingosine and a fatty acid. 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. The zinc ion within the active site 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. 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 closed conformation. 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 open conformation. The synthesis of ceramide from palmitate and sphingosine occurs via the same mechanism but in reverse. Figure 1 Proposed mechanism of ceramide hydrolysis by Inoe et al.(2009) Refs , , Disease p Relevance p Structural highlights This is a sample scene created with SAT to color by Group, and another to make a transparent representation of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.active site 2zxc is a 2 chain structure with sequence from "bacillus_aeruginosus"_(schroeter_1872)_trevisan_1885 "bacillus aeruginosus" (schroeter 1872) trevisan 1885. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 2ED, DMS, FMT, MG, ZN Activity: Ceramidase, with EC number 3.5.1.23 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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Jacob R. Mackinder, Michal Harel, Jaime Prilusky