| pubmed-article:12086582 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:12086582 | lifeskim:mentions | umls-concept:C0026882 | lld:lifeskim |
| pubmed-article:12086582 | lifeskim:mentions | umls-concept:C0007804 | lld:lifeskim |
| pubmed-article:12086582 | lifeskim:mentions | umls-concept:C0037494 | lld:lifeskim |
| pubmed-article:12086582 | lifeskim:mentions | umls-concept:C0205245 | lld:lifeskim |
| pubmed-article:12086582 | lifeskim:mentions | umls-concept:C0456378 | lld:lifeskim |
| pubmed-article:12086582 | lifeskim:mentions | umls-concept:C0392760 | lld:lifeskim |
| pubmed-article:12086582 | lifeskim:mentions | umls-concept:C0686907 | lld:lifeskim |
| pubmed-article:12086582 | pubmed:issue | Pt 2 | lld:pubmed |
| pubmed-article:12086582 | pubmed:dateCreated | 2002-10-4 | lld:pubmed |
| pubmed-article:12086582 | pubmed:abstractText | Metachromatic leukodystrophy is a lysosomal storage disorder caused by the deficiency of arylsulphatase A. We describe the functional consequences of three mis-sense mutations in the arylsulphatase A gene (Asp-335-Val, Arg-370-Trp and Arg-370-Gln), affecting an apparent intramolecular Asp-335 to Arg-370 salt bridge, and interpret the effects and clinical consequences on the basis of the three-dimensional structure of arylsulphatase A. Asp-335-Val and Arg-370-Trp substitutions each cause a complete loss of enzyme activity and are associated with the most severe form of the human disease, whereas the Arg-370-Gln-substituted enzyme retains some residual activity, being found in a patient suffering from the milder juvenile form of the disease. Detailed analysis reveals that formation of the apparent salt bridge depends critically on the presence of aspartic acid and arginine residues at positions 335 and 370, respectively. Substitution by various other amino acids, including glutamic acid and lysine, affects enzyme function severely. Biosynthesis and immunoprecipitation studies indicate that the Asp-335-Val substitution affects folding of arylsulphatase A more severely than either the Arg-370-Trp or Arg-370-Gln substitutions. In vitro mutagenesis data show that clinical severity correlates with the space occupied by residue 370. The combination with structural data suggests that the bulky tryptophan residue broadens the cleft held together by the apparent salt bridge, whereas the smaller glutamine residue still allows the cleft to close, yielding a less severely affected enzyme. The position of residue 370 in the three-dimensional structure of the enzyme provides a plausible explanation for the differing severities in loss of enzyme function caused by the mutations and thus the clinical phenotype. | lld:pubmed |
| pubmed-article:12086582 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12086582 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12086582 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:12086582 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12086582 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12086582 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12086582 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12086582 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12086582 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12086582 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12086582 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12086582 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12086582 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12086582 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12086582 | pubmed:language | eng | lld:pubmed |
| pubmed-article:12086582 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12086582 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:12086582 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12086582 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12086582 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12086582 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12086582 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12086582 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12086582 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:12086582 | pubmed:month | Oct | lld:pubmed |
| pubmed-article:12086582 | pubmed:issn | 0264-6021 | lld:pubmed |
| pubmed-article:12086582 | pubmed:author | pubmed-author:GieselmannVol... | lld:pubmed |
| pubmed-article:12086582 | pubmed:author | pubmed-author:KleinRoger... | lld:pubmed |
| pubmed-article:12086582 | pubmed:author | pubmed-author:DietzFrankF | lld:pubmed |
| pubmed-article:12086582 | pubmed:author | pubmed-author:SchestagFrank... | lld:pubmed |
| pubmed-article:12086582 | pubmed:author | pubmed-author:YaghootfamAfs... | lld:pubmed |
| pubmed-article:12086582 | pubmed:author | pubmed-author:HabethaMatthi... | lld:pubmed |
| pubmed-article:12086582 | pubmed:author | pubmed-author:PoeppelPeterP | lld:pubmed |
| pubmed-article:12086582 | pubmed:author | pubmed-author:ZlotogoraJoel... | lld:pubmed |
| pubmed-article:12086582 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:12086582 | pubmed:day | 15 | lld:pubmed |
| pubmed-article:12086582 | pubmed:volume | 367 | lld:pubmed |
| pubmed-article:12086582 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:12086582 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:12086582 | pubmed:pagination | 499-504 | lld:pubmed |
| pubmed-article:12086582 | pubmed:dateRevised | 2009-11-18 | lld:pubmed |
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| pubmed-article:12086582 | pubmed:meshHeading | pubmed-meshheading:12086582... | lld:pubmed |
| pubmed-article:12086582 | pubmed:year | 2002 | lld:pubmed |
| pubmed-article:12086582 | pubmed:articleTitle | The functional consequences of mis-sense mutations affecting an intra-molecular salt bridge in arylsulphatase A. | lld:pubmed |
| pubmed-article:12086582 | pubmed:affiliation | Institut für Physiologische Chemie, Rheinische-Friedrich-Wilhelms Universität Bonn, Nussallee 11, 53115 Bonn, Germany. | lld:pubmed |
| pubmed-article:12086582 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:12086582 | pubmed:publicationType | Case Reports | lld:pubmed |
| pubmed-article:12086582 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
