Linked Life Data

21454611

Source:http://linkedlifedata.com/resource/pubmed/id/21454611

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
24
pubmed:dateCreated
2011-6-13
pubmed:abstractText
The ?-secretase membrane protein complex is responsible for proteolytic maturation of signaling precursors and catalyzes the final step in the production of the amyloid ?-peptides implicated in the pathogenesis of Alzheimer disease. The incorporation of PEN-2 (presenilin enhancer 2) into a pre-activation intermediate, composed of the catalytic subunit presenilin and the accessory proteins APH-1 (anterior pharynx-defective 1) and nicastrin, triggers the endoproteolysis of presenilin and results in an active tetrameric ?-secretase. We have determined the three-dimensional reconstruction of a mature and catalytically active ?-secretase using single-particle cryo-electron microscopy. ?-Secretase has a cup-like shape with a lateral belt of ?40-50 Å in height that encloses a water-accessible internal chamber. Active site labeling with a gold-coupled transition state analog inhibitor suggested that the ?-secretase active site faces this chamber. Comparison with the structure of a trimeric pre-activation intermediate suggested that the incorporation of PEN-2 might contribute to the maturation of the active site architecture.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1083-351X
pubmed:author
pubmed:issnType
Electronic
pubmed:day
17
pubmed:volume
286
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
21440-9
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Structure of gamma-secretase and its trimeric pre-activation intermediate by single-particle electron microscopy.
pubmed:affiliation
Department of Structural and Chemical Biology, Mount Sinai School of Medicine, New York, New York 10029, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural