6y6t
From Proteopedia
Mouse Galactocerebrosidase complexed with galacto-noeurostegine GNS at pH 4.6
Structural highlights
DiseaseGALC_MOUSE Defects in Galc are the cause of the 'twitcher' phenotype; an autosomal recessive leukodystrophy similar to the human disease (Krabbe disease). This deficiency results in the insufficient catabolism of several galactolipids that are important in the production of normal myelin. FunctionGALC_MOUSE Hydrolyzes the galactose ester bonds of galactosylceramide, galactosylsphingosine, lactosylceramide, and monogalactosyldiglyceride. Enzyme with very low activity responsible for the lysosomal catabolism of galactosylceramide, a major lipid in myelin, kidney and epithelial cells of small intestine and colon.[1] Publication Abstract from PubMedCompetitive inhibitors of galactocerebrosidase (GALC) could be candidates for pharmacological chaperone therapy of patients with Krabbe disease. The known and selective nortropane-type iminosugar galacto-noeurostegine has been found to competitively inhibit GALC with K (i) = 7 muM at pH 4.6, which is 330-fold more potent than the analogous deoxynoeurostegine. It was shown through X-ray protein crystallography that galacto-noeurostegine binds to the active site of GALC in its bicyclic form. The Bicyclic Form of galacto-Noeurostegine Is a Potent Inhibitor of beta-Galactocerebrosidase.,Viuff A, Salamone S, McLoughlin J, Deane JE, Jensen HH ACS Med Chem Lett. 2020 Dec 18;12(1):56-59. doi: 10.1021/acsmedchemlett.0c00377. , eCollection 2021 Jan 14. PMID:33488964[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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