Ceramidase
Function‘’’CerN’’’ is an enzyme that catalyzes the cleavage of the Sphingolipid Ceramide at the N-acyl linkage, producing sphingosine and a fatty acid.[1] [2] 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. [3] [1] 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’’. [1] 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. [1] ‘’’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 openconformation. The synthesis of ceramide from palmitate and sphingosine occurs via the same mechanism, but in reverse. [1]
Diseasep[1] Relevancep Structural highlightsThis 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
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