1e33: Difference between revisions

Revision as of 00:04, 1 July 2008

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File:1e33.png

Template:STRUCTURE 1e33

CRYSTAL STRUCTURE OF AN ARYLSULFATASE A MUTANT P426LCRYSTAL STRUCTURE OF AN ARYLSULFATASE A MUTANT P426L

Template:ABSTRACT PUBMED 11777924

About this StructureAbout this Structure

1E33 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

Defective oligomerization of arylsulfatase a as a cause of its instability in lysosomes and metachromatic leukodystrophy., von Bulow R, Schmidt B, Dierks T, Schwabauer N, Schilling K, Weber E, Uson I, von Figura K, J Biol Chem. 2002 Mar 15;277(11):9455-61. Epub 2002 Jan 2. PMID:11777924

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-[[Image:1e33.gif|left|200px]]
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 {{STRUCTURE_1e33|  PDB=1e33  |  SCENE=  }}
-'''CRYSTAL STRUCTURE OF AN ARYLSULFATASE A MUTANT P426L'''
+===CRYSTAL STRUCTURE OF AN ARYLSULFATASE A MUTANT P426L===
-==Overview==
+<!--
-In one of the most common mutations causing metachromatic leukodystrophy, the P426L-allele of arylsulfatase A (ASA), the deficiency of ASA results from its instability in lysosomes. Inhibition of lysosomal cysteine proteinases protects the P426L-ASA and restores the sulfatide catabolism in fibroblasts of the patients. P426L-ASA, but not wild type ASA, was cleaved by purified cathepsin L at threonine 421 yielding 54- and 9-kDa fragments. X-ray crystallography at 2.5-A resolution showed that cleavage is not due to a difference in the protein fold that would expose the peptide bond following threonine 421 to proteases. Octamerization, which depends on protonation of Glu-424, was impaired for P426L-ASA. The mutation lowers the pH for the octamer/dimer equilibrium by 0.6 pH units from pH 5.8 to 5.2. A second oligomerization mutant (ASA-A464R) was generated that failed to octamerize even at pH 4.8. A464R-ASA was degraded in lysosomes to catalytically active 54-kDa intermediate. In cathepsin L-deficient fibroblasts, degradation of P426L-ASA and A464R-ASA to the 54-kDa fragment was reduced, while further degradation was blocked. This indicates that defective oligomerization of ASA allows degradation of ASA to a catalytically active 54-kDa intermediate by lysosomal cysteine proteinases, including cathepsin L. Further degradation of the 54-kDa intermediate critically depends on cathepsin L and is modified by the structure of the 9-kDa cleavage product.
+The line below this paragraph, {{ABSTRACT_PUBMED_11777924}}, adds the Publication Abstract to the page
+(as it appears on PubMed at http://www.pubmed.gov), where 11777924 is the PubMed ID number.
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+{{ABSTRACT_PUBMED_11777924}}
 ==About this Structure==
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 [[Category: Hydrolase]]
 [[Category: Lysosomal enzyme]]
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