8bac

Crystal structure of human heparanase in complex with competitive inhibitor GD05

spinqualitylabelsall models 8bac, resolution 2.05Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8bac is a 2 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 2.05Å Ligands: EDO, NAG, SJ5 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed 1-Azasugar analogues of l-iduronic acid (l-IdoA) and d-glucuronic acid (d-GlcA) and their corresponding enantiomers have been synthesized as potential pharmacological chaperones for mucopolysaccharidosis I (MPS I), a lysosomal storage disease caused by mutations in the gene encoding alpha-iduronidase (IDUA). The compounds were efficiently synthesized in nine or ten steps from d- or l-arabinose, and the structures were confirmed by X-ray crystallographic analysis of key intermediates. All compounds were inactive against IDUA, although l-IdoA-configured 8 moderately inhibited beta-glucuronidase (beta-GLU). The d-GlcA-configured 9 was a potent inhibitor of beta-GLU and a moderate inhibitor of the endo-beta-glucuronidase heparanase. Co-crystallization of 9 with heparanase revealed that the endocyclic nitrogen of 9 forms close interactions with both the catalytic acid and catalytic nucleophile. Synthesis of Uronic Acid 1-Azasugars as Putative Inhibitors of alpha-Iduronidase, beta-Glucuronidase and Heparanase.,Doherty GG, Ler GJM, Wimmer N, Bernhardt PV, Ashmus RA, Vocadlo DJ, Armstrong Z, Davies GJ, Maccarana M, Li JP, Kayal Y, Ferro V Chembiochem. 2023 Feb 14;24(4):e202200619. doi: 10.1002/cbic.202200619. Epub 2023 , Jan 3. PMID:36453606 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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