Linked Life Data

19399818

Source:http://linkedlifedata.com/resource/pubmed/id/19399818

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2009-5-7
pubmed:abstractText
The first solution state structural analysis (NMR) of the C-terminal sequence of human G(L) that binds to glycogen phosphorylase a (GPa), PEWPSYLGYEKLGPYY-NH(2) (1), showed it to be in a random coil conformation. This was supported by molecular dynamics simulation (modelled in solution) using NAMD 2.6. The conformational ambiguity of the peptide makes the structural arrangement of the peptide (and internal residues) strongly dependent on the environment. Thirteen tetra-peptide fragments of the C-terminal sequence, YEKLG-NH(2), and the corresponding tri- and di-peptide sequences were used in a fragment screen against GPa. Compound 2 (H-GPYY-NH(2)) did not give an IC(50) value, whereas PEWPSYLGYEKLGPYY-NH(2) (1) displayed an IC(50) of 34 microM against GPa. Truncated peptides derived from 1, (EKL-NH(2), EKLG-NH(2), and AcEKNH(2)) inhibited GPa (21%, 32%, 63%, respectively at 22 mM). These studies suggest key residues within the peptide chain have additional molecular interactions with GPa. The interaction of intra-sequence residues in combination with the terminal residues of PEWPSYLGYEKLGPYY with GPa may form the basis for the design of new inhibitors of GPa.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1099-1387
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
15
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
442-50
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Synthesis of new modified truncated peptides and inhibition of glycogen phosphorylase.
pubmed:affiliation
Eskitis Institute for Cell and Molecular Therapies, Nathan Campus, Griffith University, Brisbane, QLD, 4111, Australia.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't