Linked Life Data

19548659

Source:http://linkedlifedata.com/resource/pubmed/id/19548659

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
28
pubmed:dateCreated
2009-7-9
pubmed:abstractText
The Cu(II)-alpha-synuclein interaction has been invoked as an important process in the pathogenesis of Parkinson's disease. Herein, we report binding constants and stoichiometry under near-physiological conditions for the binding of Cu(II) to human alpha-synuclein. Specifically, we compare the binding of Cu(II) to wild-type (WT) protein and two separate single mutation proteins that are associated with familial Parkinson's diseases: A30P and A53T. Cu(II) binds to all three alpha-synuclein proteins with a 1:1 stoichiometry. The Cu(II) binding constants, however, vary among the proteins studied. Cu(II) binding to WT and A53T at 37 degrees C is similar with a pH-dependent binding constant (K) of approximately 2.4 x 10(9) and approximately 4.8 x 10(9) M(-1) at pH 7.2 and 7.4, respectively. Cu(II) binding to A30P, however, exhibits two binding constants. The major binding site of A30P, characteristic of >90% of the bound Cu(II), has binding constants of 1.6 x 10(9) and 3.6 x 10(9) M(-1) at pH 7.2 and 7.4, respectively, slightly lower ( approximately 70%) than that characteristic of WT or A53T at the corresponding pH. The second less populated binding exhibited by A30P has a large binding constant, approximately 10(10) M(-1). Our size exclusion analysis ruled out the contribution of protofibrils to the strong Cu(II) binding. Previous studies indicated that A30P had a larger proportion of intermediate species (e.g., small oligomeric species, such as dimers and trimers) relative to WT and A53T. Thus, we propose that the high affinity site is attributed to the binding of Cu(II) to those small oligomeric species.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1520-6106
pubmed:author
pubmed:issnType
Print
pubmed:day
16
pubmed:volume
113
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
9551-61
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Binding of Cu(II) to human alpha-synucleins: comparison of wild type and the point mutations associated with the familial Parkinson's disease.
pubmed:affiliation
Department of Chemistry, Duke University, Durham, NC 27708, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't