2vc9

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{{STRUCTURE_2vc9| PDB=2vc9 | SCENE= }}
{{STRUCTURE_2vc9| PDB=2vc9 | SCENE= }}
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'''FAMILY 89 GLYCOSIDE HYDROLASE FROM CLOSTRIDIUM PERFRINGENS IN COMPLEX WITH 2-ACETAMIDO-1,2-DIDEOXYNOJIRMYCIN'''
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===FAMILY 89 GLYCOSIDE HYDROLASE FROM CLOSTRIDIUM PERFRINGENS IN COMPLEX WITH 2-ACETAMIDO-1,2-DIDEOXYNOJIRMYCIN===
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==Overview==
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Mucopolysaccharidosis III (MPS III) has four forms (A-D) that result from buildup of an improperly degraded glycosaminoglycan in lysosomes. MPS IIIB is attributable to the decreased activity of a lysosomal alpha-N-acetylglucosaminidase (NAGLU). Here, we describe the structure, catalytic mechanism, and inhibition of CpGH89 from Clostridium perfringens, a close bacterial homolog of NAGLU. The structure enables the generation of a homology model of NAGLU, an enzyme that has resisted structural studies despite having been studied for &gt;20 years. This model reveals which mutations giving rise to MPS IIIB map to the active site and which map to regions distant from the active site. The identification of potent inhibitors of CpGH89 and the structures of these inhibitors in complex with the enzyme suggest small-molecule candidates for use as chemical chaperones. These studies therefore illuminate the genetic basis of MPS IIIB, provide a clear biochemical rationale for the necessary sequential action of heparan-degrading enzymes, and open the door to the design and optimization of chemical chaperones for treating MPS IIIB.
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{{ABSTRACT_PUBMED_18443291}}
==About this Structure==
==About this Structure==
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[[Category: Naglu]]
[[Category: Naglu]]
[[Category: Sanfilippo disease]]
[[Category: Sanfilippo disease]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed May 14 11:39:40 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 08:32:09 2008''

Revision as of 05:32, 28 July 2008

Image:2vc9.png

Template:STRUCTURE 2vc9

FAMILY 89 GLYCOSIDE HYDROLASE FROM CLOSTRIDIUM PERFRINGENS IN COMPLEX WITH 2-ACETAMIDO-1,2-DIDEOXYNOJIRMYCIN

Template:ABSTRACT PUBMED 18443291

About this Structure

2VC9 is a Single protein structure of sequence from Clostridium perfringens. Full crystallographic information is available from OCA.

Reference

Structural and mechanistic insight into the basis of mucopolysaccharidosis IIIB., Ficko-Blean E, Stubbs KA, Nemirovsky O, Vocadlo DJ, Boraston AB, Proc Natl Acad Sci U S A. 2008 May 6;105(18):6560-5. Epub 2008 Apr 28. PMID:18443291

Page seeded by OCA on Mon Jul 28 08:32:09 2008

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