5fc1 | pdb_00005fc1

Murine SMPDL3A in complex with sulfate

spinqualitylabelsall models 5fc1, resolution 1.39Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5fc1 is a 1 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.389Å Ligands: BMA, FUC, GOL, MAN, NAG, SO4, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ASM3A_MOUSE Publication Abstract from PubMed Sphingomyelin phosphodiesterase, acid-like 3A (SMPDL3A) is a member of a small family of proteins founded by the well-characterized lysosomal enzyme, acid sphingomyelinase (ASM, ASMase). ASMase converts sphingomyelin (SM) into the signaling lipid, ceramide. It was recently discovered that, in contrast to ASMase, SMPDL3A is inactive against SM and, surprisingly, can instead hydrolyze nucleoside diphosphates and triphosphates, which may play a role in purinergic signaling. As none of the ASMase-like proteins have been structurally characterized to date, the molecular basis for their substrate preferences are unknown. Here we report crystal structures of murine SMPDL3A, which represent the first structures of an ASMase-like protein. The catalytic domain consists of a central mixed beta-sandwich surrounded by alpha-helices. Additionally, SMPDL3A possesses a unique C-terminal domain formed from a cluster of four alpha-helices that appears to distinguish this protein family from other phosphoesterases. We show that SMDPL3A is a di-zinc-dependent enzyme with an active site configuration that suggests a mechanism of phosphodiester hydrolysis by a metal-activated water molecule and protonation of the leaving group by a histidine residue. Co-crystal structures of SMPDL3A with AMP and alpha,beta-methylene ADP (AMPCP) reveal that the substrate binding site accommodates nucleotides by establishing interactions with their base, sugar and phosphate moieties, with the latter being the major contributor to binding affinity. Our study provides the structural basis for SMPDL3A substrate specificity and sheds new light on the function of ASMase-like proteins. Structural Basis for Nucleotide Hydrolysis by the Acid Sphingomyelinase-Like Phosphodiesterase SMPDL3A.,Gorelik A, Illes K, Superti-Furga G, Nagar B J Biol Chem. 2016 Jan 20. pii: jbc.M115.711085. PMID:26792860 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Sphingomyelinase

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