Linked Life Data

3135406

Source:http://linkedlifedata.com/resource/pubmed/id/3135406

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
1988-9-2
pubmed:abstractText
Substrate analogues based on the amino acid sequence of the hinge region of human IgA1 around the cleavage site of the IgA1 proteinases secreted by Neisseria gonorrhoeae are competitive inhibitors of these enzymes. The octapeptide Thr-Pro-Pro-Thr-Pro-Ser-Pro-Ser, which occurs between residues 233 and 240, has an IC50 value of 0.26 mM for the type 1 proteinase and 0.50 mM for the type 2 enzyme. Acetylation of the octapeptide N-terminal amino group lowers affinity for the type 1 proteinase sixfold but does not change binding to the type 2 enzyme. Amidation of the C-terminal carboxyl group does not change binding to the type 1 proteinase but improves IC50 for the type 2 enzyme. Simultaneous blockade of both the N- and C-termini drastically lowers affinity of the octapeptide for both proteinases. Sequential replacement of the hydroxy amino acids in the blocked octapeptide with cysteine yields a series of inhibitors that generally bind to the neisserial IgA1 proteinases as well as or better than the unblocked octapeptide. The most effective inhibitor contains a cysteine residue at position 6 (P3') and has an IC50 value for the type 2 IgA1 proteinase of 50 microM. Dimerization of the cysteine-containing octapeptides significantly diminishes inhibitory properties. The substrate analogues described here are the first synthetic inhibitors of the neisserial IgA1 proteinases to be reported.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:volume
31
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1647-51
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1988
pubmed:articleTitle
Substrate analogue inhibitors of the IgA1 proteinases from Neisseria gonorrhoeae.
pubmed:affiliation
Evans Memorial Department of Clinical Research, University Hospital, Boston, Massachusetts 02118.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.