Linked Life Data

16835244

Source:http://linkedlifedata.com/resource/pubmed/id/16835244

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
36
pubmed:dateCreated
2006-9-4
pubmed:abstractText
Necrotic is a member of the serine protease inhibitor or serpin superfamily. It is a potent inhibitor of elastase and chymotrypsin type proteases and is responsible for regulating the anti-fungal response in Drosophila melanogaster. Necrotic contains three basic lysine residues within the D-helix that are homologous to those found in the heparin-binding domain of antithrombin and heparin co-factor II. We show here that substitution of all three lysine residues for glutamines caused cellular necrosis and premature death in Drosophila in keeping with a loss of function phenotype. The lysine to glutamine substitutions had no effect on the overall structure of recombinant Necrotic protein but abolished the formation of stable complexes with target proteases. Individual substitutions with either glutamine or alanine demonstrated that lysine 68 was the most critical residue for inhibitory activity. Despite the homology to other serpins, Necrotic did not bind, nor was it activated by sulfated glycans. These data demonstrate a critical role for basic residues within the D-helix (and lysine 68 in particular) in the inhibitory mechanism of the serpin Necrotic.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
8
pubmed:volume
281
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
26437-43
pubmed:dateRevised
2007-8-13
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Inhibitory activity of the Drosophila melanogaster serpin Necrotic is dependent on lysine residues in the D-helix.
pubmed:affiliation
Department of Genetics, University of Cambridge, Cambridge CB2 3EH, United Kingdom.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't