Linked Life Data

11880376

Source:http://linkedlifedata.com/resource/pubmed/id/11880376

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
19
pubmed:dateCreated
2002-5-6
pubmed:abstractText
Familial encephalopathy with neuroserpin inclusion bodies (FENIB) is an autosomal dominant dementia that is characterized by intraneuronal inclusions of mutant neuroserpin. We report here the expression, purification, and characterization of wild-type neuroserpin and neuroserpin containing the S49P mutation that causes FENIB. Wild-type neuroserpin formed SDS-stable complexes with tPA with an association rate constant and K(i) of 1.2 x 10(4) m(-1) s(-1) and 5.8 nm, respectively. In contrast, S49P neuroserpin formed unstable complexes with an association rate constant and K(i) of 0.3 x 10(4) m(-1) s(-1) and 533.3 nm, respectively. An assessment by circular dichroism showed that S49P neuroserpin had a lower melting temperature than wild-type protein (49.9 and 56.6 degrees C, respectively) and more readily formed loop-sheet polymers under physiological conditions. Neither the wild-type nor S49P neuroserpin accepted the P7-P2 alpha(1)-anti-trypsin or P14-P3 antithrombin-reactive loop peptides that have been shown to block polymer formation in other members of the serpin superfamily. Taken together, these data demonstrate that S49P neuroserpin is a poor proteinase inhibitor and readily forms loop-sheet polymers. These findings provide strong support for the role of neuroserpin polymerization in the formation of the intraneuronal inclusions that are characteristic of FENIB.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
10
pubmed:volume
277
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
17367-73
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Mutant Neuroserpin (S49P) that causes familial encephalopathy with neuroserpin inclusion bodies is a poor proteinase inhibitor and readily forms polymers in vitro.
pubmed:affiliation
Respiratory Medicine Unit and Neurology Unit, Department of Medicine, University of Cambridge, Cambridge Institute for Medical Research, Wellcome Trust/Medical Research Council Building, United Kingdom. db301@cam.ac.uk
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't