2nt0
From Proteopedia
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Acid-beta-glucosidase low pH, glycerol bound
Contents |
Overview
Gaucher disease results from mutations in the lysosomal enzyme acid, beta-glucosidase (GCase). Although enzyme replacement therapy has improved, the health of some affected individuals, such as those with the prevalent, N370S mutation, oral treatment with pharmacological chaperones may be, therapeutic in a wider range of tissue compartments by restoring, sufficient activity of endogenous mutant GCase. Here we demonstrate that, isofagomine (IFG, 1) binds to the GCase active site, and both increases, GCase activity in cell lysates and restores lysosomal trafficking in cells, containing N370S mutant GCase. We also compare the crystal structures of, IFG-bound GCase at low pH with those of glycerol-bound GCase at low pH and, apo-GCase at neutral pH. Our data indicate that IFG induces active GCase, which is secured by interactions with Asn370. The design of small, molecules that stabilize substrate-bound conformations of mutant proteins, may be a general therapeutic strategy for diseases caused by protein, misfolding and mistrafficking.
Disease
Known diseases associated with this structure: Gaucher disease, perinatal lethal OMIM:[606463], Gaucher disease, type I OMIM:[606463], Gaucher disease, type II OMIM:[606463], Gaucher disease, type III OMIM:[606463], Gaucher disease, type IIIC OMIM:[606463], Graves disease, susceptibility to, 3 OMIM:[139200]
About this Structure
2NT0 is a Single protein structure of sequence from Homo sapiens with , and as ligands. Active as Glucosylceramidase, with EC number 3.2.1.45 Full crystallographic information is available from OCA.
Reference
Structure of acid beta-glucosidase with pharmacological chaperone provides insight into Gaucher disease., Lieberman RL, Wustman BA, Huertas P, Powe AC Jr, Pine CW, Khanna R, Schlossmacher MG, Ringe D, Petsko GA, Nat Chem Biol. 2007 Feb;3(2):101-7. Epub 2006 Dec 24. PMID:17187079
Page seeded by OCA on Fri Feb 15 17:39:42 2008
