Linked Life Data

20674745

Source:http://linkedlifedata.com/resource/pubmed/id/20674745

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2010-9-20
pubmed:abstractText
We have carried out an extensive in silico analysis on 18 disease associated missense mutations found in electron transfer flavoprotein (ETF), and found that mutations fall essentially in two groups, one in which mutations affect protein folding and assembly, and another one in which mutations impair catalytic activity and disrupt interactions with partner dehydrogenases. We have further experimentally analyzed three of these mutations, ETF?-p.Cys42Arg, ETF?-p.Asp128Asn and ETF?-p.Arg191Cys, which have been found in homozygous form in patients and which typify different scenarios in respect to the clinical phenotypes. The ETF?-p.Cys42Arg mutation, related to a severe form of multiple acyl-CoA dehydrogenase deficiency (MADD), affects directly the AMP binding site and intersubunit contacts and impairs correct protein folding. The two other variations, ETF?-p.Asp128Asn and ETF?-p.Arg191Cys, are both associated with mild MADD, but these mutations have a different impact on ETF. Although none affects the overall ?/? fold topology as shown by far-UV CD, analysis of the purified proteins shows that both have substantially decreased enzymatic activity and conformational stability. Altogether, this study combines in silico analysis of mutations with experimental data and has allowed establishing structural hotspots within the ETF fold that are useful to provide a rationale for the prediction of effects of mutations in ETF.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0006-3002
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 Elsevier B.V. All rights reserved.
pubmed:issnType
Print
pubmed:volume
1802
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1070-7
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Mutational hotspots in electron transfer flavoprotein underlie defective folding and function in multiple acyl-CoA dehydrogenase deficiency.
pubmed:affiliation
Instituto Tecnologia Química e Biológica, Universidade Nova de Lisboa, Oeiras, Portugal.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't