5u81

Acid ceramidase (ASAH1, aCDase) from naked mole rat, Cys143Ala, uncleaved

spinqualitylabelsall models 5u81, resolution 1.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5u81 is a 1 chain structure with sequence from Heterocephalus glaber. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.4Å Ligands: 1PE, BMA, CL, FUC, GOL, MAN, NAG, PG4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function G5AP74_HETGA Publication Abstract from PubMed Acid ceramidase (aCDase, ASAH1) hydrolyzes lysosomal membrane ceramide into sphingosine, the backbone of all sphingolipids, to regulate many cellular processes. Abnormal function of aCDase leads to Farber disease, spinal muscular atrophy with progressive myoclonic epilepsy, and is associated with Alzheimer's, diabetes, and cancer. Here, we present crystal structures of mammalian aCDases in both proenzyme and autocleaved forms. In the proenzyme, the catalytic center is buried and protected from solvent. Autocleavage triggers a conformational change exposing a hydrophobic channel leading to the active site. Substrate modeling suggests distinct catalytic mechanisms for substrate hydrolysis versus autocleavage. A hydrophobic surface surrounding the substrate binding channel appears to be a site of membrane attachment where the enzyme accepts substrates facilitated by the accessory protein, saposin-D. Structural mapping of disease mutations reveals that most would destabilize the protein fold. These results will inform the rational design of aCDase inhibitors and recombinant aCDase for disease therapeutics. Structural basis for the activation of acid ceramidase.,Gebai A, Gorelik A, Li Z, Illes K, Nagar B Nat Commun. 2018 Apr 24;9(1):1621. doi: 10.1038/s41467-018-03844-2. PMID:29692406 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ceramidase 3D PDB structures

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