FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1973556303> ?p ?o ?g. }

• W1973556303 abstract "Abstract Background GPR17 is a hybrid G-protein-coupled receptor (GPCR) activated by two unrelated ligand families, extracellular nucleotides and cysteinyl-leukotrienes (cysteinyl-LTs), and involved in brain damage and repair. Its exploitment as a target for novel neuro-reparative strategies depends on the elucidation of the molecular determinants driving binding of purinergic and leukotrienic ligands. Here, we applied docking and molecular dynamics simulations (MD) to analyse the binding and the forced unbinding of two GPR17 ligands (the endogenous purinergic agonist UDP and the leukotriene receptor antagonist pranlukast from both the wild-type (WT) receptor and a mutant model, where a basic residue hypothesized to be crucial for nucleotide binding had been mutated (R255I) to Ile. Results MD suggested that GPR17 nucleotide binding pocket is enclosed between the helical bundle and extracellular loop (EL) 2. The driving interaction involves R255 and the UDP phosphate moiety. To support this hypothesis, steered MD experiments showed that the energy required to unbind UDP is higher for the WT receptor than for R255I. Three potential binding sites for pranlukast where instead found and analysed. In one of its preferential docking conformations, pranlukast tetrazole group is close to R255 and phenyl rings are placed into a subpocket highly conserved among GPCRs. Pulling forces developed to break polar and aromatic interactions of pranlukast were comparable. No differences between the WT receptor and the R255I receptor were found for the unbinding of pranlukast. Conclusions These data thus suggest that, in contrast to which has been hypothesized for nucleotides, the lack of the R255 residue doesn't affect the binding of pranlukast a crucial role for R255 in binding of nucleotides to GPR17. Aromatic interactions are instead likely to play a predominant role in the recognition of pranlukast, suggesting that two different binding subsites are present on GPR17." @default.
• W1973556303 created "2016-06-24" @default.
• W1973556303 creator A5033111103 @default.
• W1973556303 creator A5051881392 @default.
• W1973556303 creator A5062628094 @default.
• W1973556303 creator A5088903530 @default.
• W1973556303 date "2010-03-16" @default.
• W1973556303 modified "2023-09-25" @default.
• W1973556303 title "Forced unbinding of GPR17 ligands from wild type and R255I mutant receptor models through a computational approach" @default.
• W1973556303 cites W1572609533 @default.
• W1973556303 cites W1825353903 @default.
• W1973556303 cites W1833104430 @default.
• W1973556303 cites W1908561802 @default.
• W1973556303 cites W1966252693 @default.
• W1973556303 cites W1967490656 @default.
• W1973556303 cites W1967903432 @default.
• W1973556303 cites W1972923838 @default.
• W1973556303 cites W1973240518 @default.
• W1973556303 cites W1974468894 @default.
• W1973556303 cites W1975740938 @default.
• W1973556303 cites W1979166300 @default.
• W1973556303 cites W1983362126 @default.
• W1973556303 cites W1985320691 @default.
• W1973556303 cites W1985900564 @default.
• W1973556303 cites W1987656345 @default.
• W1973556303 cites W1988661280 @default.
• W1973556303 cites W1990189572 @default.
• W1973556303 cites W1995659307 @default.
• W1973556303 cites W1996401334 @default.
• W1973556303 cites W1997332036 @default.
• W1973556303 cites W1997884817 @default.
• W1973556303 cites W1998640237 @default.
• W1973556303 cites W2006853049 @default.
• W1973556303 cites W2012121740 @default.
• W1973556303 cites W2021213286 @default.
• W1973556303 cites W2021497244 @default.
• W1973556303 cites W2021914752 @default.
• W1973556303 cites W2025842794 @default.
• W1973556303 cites W2027003344 @default.
• W1973556303 cites W2032143666 @default.
• W1973556303 cites W2034941411 @default.
• W1973556303 cites W2041566506 @default.
• W1973556303 cites W2042170152 @default.
• W1973556303 cites W2046208572 @default.
• W1973556303 cites W2046826628 @default.
• W1973556303 cites W2047314546 @default.
• W1973556303 cites W2050417355 @default.
• W1973556303 cites W2051514715 @default.
• W1973556303 cites W2058573636 @default.
• W1973556303 cites W2064291209 @default.
• W1973556303 cites W2067902409 @default.
• W1973556303 cites W2069466107 @default.
• W1973556303 cites W2073898713 @default.
• W1973556303 cites W2079197830 @default.
• W1973556303 cites W2080231167 @default.
• W1973556303 cites W2080559139 @default.
• W1973556303 cites W2087584115 @default.
• W1973556303 cites W2090403872 @default.
• W1973556303 cites W2094589918 @default.
• W1973556303 cites W2096550848 @default.
• W1973556303 cites W2100147128 @default.
• W1973556303 cites W2100201978 @default.
• W1973556303 cites W2100452437 @default.
• W1973556303 cites W2104477830 @default.
• W1973556303 cites W2104559182 @default.
• W1973556303 cites W2105614327 @default.
• W1973556303 cites W2106327430 @default.
• W1973556303 cites W2109014958 @default.
• W1973556303 cites W2114103296 @default.
• W1973556303 cites W2115342107 @default.
• W1973556303 cites W2122308713 @default.
• W1973556303 cites W2123768693 @default.
• W1973556303 cites W2128572087 @default.
• W1973556303 cites W2132354058 @default.
• W1973556303 cites W2133593302 @default.
• W1973556303 cites W2135689740 @default.
• W1973556303 cites W2137588110 @default.
• W1973556303 cites W2139065407 @default.
• W1973556303 cites W2147749191 @default.
• W1973556303 cites W2152410026 @default.
• W1973556303 cites W2154071625 @default.
• W1973556303 cites W2154421695 @default.
• W1973556303 cites W2158534713 @default.
• W1973556303 cites W2166367654 @default.
• W1973556303 cites W2170298332 @default.
• W1973556303 cites W2171268876 @default.
• W1973556303 cites W2432510279 @default.
• W1973556303 cites W2626246102 @default.
• W1973556303 cites W3150248096 @default.
• W1973556303 cites W4243050019 @default.
• W1973556303 doi "https://doi.org/10.1186/1472-6807-10-8" @default.
• W1973556303 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2850907" @default.
• W1973556303 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/20233425" @default.
• W1973556303 hasPublicationYear "2010" @default.
• W1973556303 type Work @default.
• W1973556303 sameAs 1973556303 @default.
• W1973556303 citedByCount "27" @default.
• W1973556303 countsByYear W19735563032012 @default.
• W1973556303 countsByYear W19735563032013 @default.
• W1973556303 countsByYear W19735563032014 @default.

• next