2nt1
From Proteopedia
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==About this Structure== | ==About this Structure== | ||
| - | 2NT1 is a | + | 2NT1 is a 4 chains structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NT1 OCA]. |
==Reference== | ==Reference== | ||
| - | + | <ref group="xtra">PMID:17187079</ref><references group="xtra"/> | |
[[Category: Glucosylceramidase]] | [[Category: Glucosylceramidase]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
| - | [[Category: Single protein]] | ||
[[Category: Lieberman, R L.]] | [[Category: Lieberman, R L.]] | ||
[[Category: Petsko, G A.]] | [[Category: Petsko, G A.]] | ||
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[[Category: Glucosylceramide]] | [[Category: Glucosylceramide]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Feb 18 04:42:36 2009'' |
Revision as of 02:42, 18 February 2009
Contents |
Structure of acid-beta-glucosidase at neutral pH
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.
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
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Disease
Known disease 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]
About this Structure
2NT1 is a 4 chains structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
- Lieberman RL, Wustman BA, Huertas P, Powe AC Jr, Pine CW, Khanna R, Schlossmacher MG, Ringe D, Petsko GA. Structure of acid beta-glucosidase with pharmacological chaperone provides insight into Gaucher disease. Nat Chem Biol. 2007 Feb;3(2):101-7. Epub 2006 Dec 24. PMID:17187079 doi:http://dx.doi.org/10.1038/nchembio850
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