Linked Life Data

15800373

Source:http://linkedlifedata.com/resource/pubmed/id/15800373

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2005-3-31
pubmed:abstractText
That the zinc metalloendopeptidase insulysin (insulin-degrading enzyme IDE) is a major b-amyloid (A(beta)) peptide-degrading enzyme in vivo is shown by the higher A(beta) peptide levels in the brain of an insulysin-deficient mouse. Insulysin was shown to initially cleave A(beta)1-40and A(beta)1-42 at His13-Gln14, His14-Gln15, and Phe19-Phe20. The insulysin-dependent cleavage of A(beta) prevents both the neurotoxic effects of the peptide as well as the ability of A(beta) to deposit onto synthetic amyloid plaques. The kinetics of the reaction of insulysin with the synthetic peptide substrate Abz-G-G-F-L-R-K-H-G-Q-EDDnp displays allosteric properties indicative of a regulated enzyme. Small peptide substrates increase the activity of insulysin toward the hydrolysis of A(beta)1-40 without affecting the activity of the enzyme toward insulin. These studies indicate that insulysin is a target for drug development in which small-molecule peptide analogs can be used to increase the rate of A(beta) clearance without affecting insulin levels.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0895-8696
pubmed:author
pubmed:issnType
Print
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
201-6
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Insulysin: an allosteric enzyme as a target for Alzheimer's disease.
pubmed:affiliation
Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY 40536, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural