5udy

Human alkaline sphingomyelinase (alk-SMase, ENPP7, NPP7)

spinqualitylabelsall models 5udy, resolution 2.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5udy is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: FUC, IOD, NA, NAG, ZN Gene: ENPP7, UNQ3077/PRO9912 (HUMAN) Activity: Sphingomyelin phosphodiesterase, with EC number 3.1.4.12 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [ENPP7_HUMAN] Converts sphingomyelin to ceramide. Also has phospholipase C activity toward palmitoyl lyso-phosphocholine. Does not appear to have nucleotide pyrophosphatase activity. Publication Abstract from PubMed Absorption of dietary sphingomyelin (SM) requires its initial degradation into ceramide, a process catalyzed by the intestinal enzyme alkaline sphingomyelinase (alk-SMase, NPP7, ENPP7). Alk-SMase belongs to the nucleotide pyrophosphatase / phosphodiesterase family, the members of which hydrolyze nucleoside phosphates, phospholipids and other related molecules. NPP7 is the only paralog that can cleave SM, and its activity requires the presence of bile salts, a class of physiological anionic detergents. To elucidate the mechanism of substrate recognition, we determined the crystal structure of human alk-SMase in complex with phosphocholine, a reaction product. Although the overall fold and catalytic center is conserved relative to other NPPs, alk-SMase recognizes the choline moiety of its substrates via an NPP7-specific aromatic box composed of tyrosine residues. Mutational analysis and enzymatic activity assays identified features on the surface of the protein - a cationic patch and a unique hydrophobic loop - that are essential for accessing SM in bile salt micelles. These results shed new light on substrate specificity determinants within the NPP enzyme family. Crystal Structure of the Human Alkaline Sphingomyelinase Provides Insights into Substrate Recognition.,Gorelik A, Liu F, Illes K, Nagar B J Biol Chem. 2017 Mar 14. pii: jbc.M116.769273. doi: 10.1074/jbc.M116.769273. PMID:28292932 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ectonucleotide pyrophosphatase/phosphodiesterase 3D structures Sphingomyelinase

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