Linked Life Data

9128441

Source:http://linkedlifedata.com/resource/pubmed/id/9128441

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
1997-5-21
pubmed:abstractText
Double-tailed lipo-tetragastrin derivatives of increasing fatty acid chain length were used to identify the minimum size of the fatty acid moieties (> or = C10) that restricts the access to the CCK-B/gastrin (CCK: cholecystokinin) receptor via a membrane-bound pathway. Then dimyristoyl-mercaptoglycerol/maleoyl-gastrin adducts of increasing peptide chain length were synthesized to define the minimal peptide size required for receptor binding affinities comparable, to those of underivatized gastrin peptides despite anchorage of the lipid tails in the membrane bilayer. The experimental results indicated that most of the little-gastrin sequence, i.e., 2-17, is needed for optimal interaction of the molecule with the binding cleft of the receptor. From these data experimentally based restraints could be derived for docking of lipo-gastrin onto a CCK-B/gastrin receptor model applying molecular dynamics simulations and energy minimizations. In the receptor-bound state some of the secondary structure elements of gastrin as determined by nmr analysis of gastrin-peptides in low dielectric constant media are retained. The N-terminal gastrin portion interacts in a more or less extended conformation with the receptor surface, and upon a sharp kink at the Ala-Tyr dipeptide portion the C-terminal pentapeptide amide part inserts deeply into the helix bundle. Besides Arg-57 on top of helix 1 of the receptor, for which no potential interaction with the ligand could be detected, the other amino acid residues identified by mutagenesis studies as involved in gastrin recognition were found to interact with the C-terminal portion of gastrin. Even taking into account the strong limitations of such a model system, it represents an interesting tool for rationalizing the experimental results of the extensive structure-function studies performed previously on gastrin and to delineate more precisely the putative ligand binding site on the extracellular face of the receptor.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0006-3525
pubmed:author
pubmed:issnType
Print
pubmed:volume
41
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
799-817
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Mapping of ligand binding sites of the cholecystokinin-B/gastrin receptor with lipo-gastrin peptides and molecular modeling.
pubmed:affiliation
Max-Planck-Institut für Biochemie, Martinsried, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't