Linked Life Data

19053519

Source:http://linkedlifedata.com/resource/pubmed/id/19053519

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2008-12-22
pubmed:abstractText
The binding of phosphorylated peptides to the receptor plays a major role in many basic cellular processes in a variety of pathological states. Human beta-TrCP is a key component of a recently characterized E3 ubiquitin ligase complex that regulates protein degradation through the ubiquitin-dependent proteasome pathway. Docking studies were carried out to explore the structural requirements for the beta-TrCP substrates. Docking studies were performed on the bound conformation of the phosphorylated peptides determined by NMR, whereas the beta-TrCP structure was derived by X-ray from Protein Data Bank. After the docking calculation, during which the peptides were conformationally restrained, the complex presented herein was analyzed in terms of ligand-protein interactions and properties of contacting surfaces. The structural requirements for phosphorylated substrates in interaction with beta-TrCP were explored and compared with experimental data from TRNOESY and STD NMR results. The analysis revealed that the bend of the peptide structures, which is indispensable for beta-TrCP recognition, aligns two charged phosphate groups and a central hydrophobic group in a favorable arrangement that leads to the burial of the peptide surface in the binding cleft upon complexation. Through docking simulations, we have identified different specific binding pockets of beta-TrCP according to the ligand in interaction. These data should be valuable in the rational design of a ligand to be used in therapeutic approaches.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1549-9596
pubmed:author
pubmed:issnType
Print
pubmed:volume
48
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2350-61
pubmed:meshHeading
pubmed-meshheading:19053519-Amino Acid Sequence, pubmed-meshheading:19053519-Catalytic Domain, pubmed-meshheading:19053519-Computer Simulation, pubmed-meshheading:19053519-Consensus Sequence, pubmed-meshheading:19053519-Crystallography, X-Ray, pubmed-meshheading:19053519-Humans, pubmed-meshheading:19053519-Ligands, pubmed-meshheading:19053519-Macromolecular Substances, pubmed-meshheading:19053519-Models, Molecular, pubmed-meshheading:19053519-Molecular Sequence Data, pubmed-meshheading:19053519-Nuclear Magnetic Resonance, Biomolecular, pubmed-meshheading:19053519-Peptides, pubmed-meshheading:19053519-Phosphorylation, pubmed-meshheading:19053519-SKP Cullin F-Box Protein Ligases, pubmed-meshheading:19053519-Sequence Homology, Amino Acid, pubmed-meshheading:19053519-Substrate Specificity, pubmed-meshheading:19053519-beta Catenin
pubmed:year
2008
pubmed:articleTitle
Structure of the complex between phosphorylated substrates and the SCF beta-TrCP ubiquitin ligase receptor: a combined NMR, molecular modeling, and docking approach.
pubmed:affiliation
Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, Universite Paris Descartes, UMR 8601-CNRS, 45 rue des Saint-Peres, 75006 Paris, France.
pubmed:publicationType
Journal Article, In Vitro