6mhm

Crystal structure of human acid ceramidase in covalent complex with carmofur

spinqualitylabelsall models 6mhm, resolution 2.74Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6mhm is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.743Å Ligands: JRY, NAG, PRD_900017, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Human acid ceramidase (AC) is a lysosomal cysteine amidase, which has received a great deal of interest in recent years as a potential target for the development of new therapeutics against melanoma and glioblastoma tumors. Despite the strong interest in obtaining structural information, only the structures of the apo-AC enzyme in its zymogen and activated conformations are available. In this work, the crystal structure of AC in complex with the covalent carmofur inhibitor is presented. Carmofur is an antineoplastic drug containing an electrophilic carbonyl reactive group that targets the catalytic cysteine. This novel structural data explains the basis of the AC inhibition, provides insights into the enzymatic properties of the protein, and is a great aid toward the structure-based drug design of potent inhibitors for AC, providing the detailed mechanism, which has eluded the scientific community for more than 30 years, of carmofur's mysterious 5-fluorouracil-independent antitumor activity. Molecular Mechanism of Inhibition of Acid Ceramidase by Carmofur.,Dementiev A, Joachimiak A, Nguyen H, Gorelik A, Illes K, Shabani S, Gelsomino M, Ahn EE, Nagar B, Doan N J Med Chem. 2019 Jan 24;62(2):987-992. doi: 10.1021/acs.jmedchem.8b01723. Epub, 2018 Dec 19. PMID:30525581 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ceramidase 3D PDB structures

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