| pubmed-article:17942747 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:17942747 | lifeskim:mentions | umls-concept:C0020792 | lld:lifeskim |
| pubmed-article:17942747 | lifeskim:mentions | umls-concept:C1517880 | lld:lifeskim |
| pubmed-article:17942747 | lifeskim:mentions | umls-concept:C1709915 | lld:lifeskim |
| pubmed-article:17942747 | lifeskim:mentions | umls-concept:C0679622 | lld:lifeskim |
| pubmed-article:17942747 | lifeskim:mentions | umls-concept:C0205314 | lld:lifeskim |
| pubmed-article:17942747 | lifeskim:mentions | umls-concept:C1451074 | lld:lifeskim |
| pubmed-article:17942747 | pubmed:issue | 1 | lld:pubmed |
| pubmed-article:17942747 | pubmed:dateCreated | 2007-12-20 | lld:pubmed |
| pubmed-article:17942747 | pubmed:abstractText | Delineation of peptide ligand binding sites is of fundamental importance in rational drug design and in understanding ligand-induced receptor activation. Molecular modeling and ligand docking to previously experimentally identified binding sites revealed a putative novel interaction between the C terminus of gonadotropin-releasing hormone (GnRH) and Arg(38(1.35)), located at the extracellular end of transmembrane domain 1 of the human GnRH receptor. Mutation of Arg(38(1.35)) to alanine resulted in 989- and 1268-fold reduction in affinity for GnRH I and GnRH II, respectively, the two endogenous ligands. Conservative mutation of Arg(38(1.35)) to lysine had less effect, giving reduced affinities of GnRH I and GnRH II by 24- and 54-fold, respectively. To test whether Arg(38(1.35)) interacts with the C-terminal Gly(10)-NH(2) of GnRH, binding of GnRH analogs with substitution of the C-terminal glycinamide with ethylamide ([Pro(9)-NHEt]GnRH) was studied with wild-type and Arg(38(1.35)) mutant receptors. Mutation of Arg(38(1.35)) to lysine or alanine had much smaller effect on receptor affinity for [Pro(9)-NHEt]GnRH analogs and no effect on binding affinity of peptide antagonist cetrorelix. In parallel with the decreased affinity, the mutants also gave a decreased potency to GnRH-elicited inositol phosphate (IP) responses. The mutant receptors had effects on [Pro(9)-NHEt]GnRH-elicited IP responses similar to that of the parent GnRHs. These findings indicate that Arg(38(1.35)) of the GnRH receptor is essential for high-affinity binding of GnRH agonists and stabilizing the receptor active conformation. The mutagenesis results support the prediction of molecular modeling that Arg(38(1.35)) interacts with the C-terminal glycinamide and probably forms hydrogen bonds with the backbone carbonyl of Pro(9) and Gly(10)-NH(2). | lld:pubmed |
| pubmed-article:17942747 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17942747 | pubmed:language | eng | lld:pubmed |
| pubmed-article:17942747 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17942747 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:17942747 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17942747 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17942747 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17942747 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:17942747 | pubmed:month | Jan | lld:pubmed |
| pubmed-article:17942747 | pubmed:issn | 1521-0111 | lld:pubmed |
| pubmed-article:17942747 | pubmed:author | pubmed-author:MillarRobert... | lld:pubmed |
| pubmed-article:17942747 | pubmed:author | pubmed-author:LuZhi-LiangZL | lld:pubmed |
| pubmed-article:17942747 | pubmed:author | pubmed-author:SellarRobinR | lld:pubmed |
| pubmed-article:17942747 | pubmed:author | pubmed-author:StewartAlan... | lld:pubmed |
| pubmed-article:17942747 | pubmed:author | pubmed-author:WilsonDonald... | lld:pubmed |
| pubmed-article:17942747 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:17942747 | pubmed:volume | 73 | lld:pubmed |
| pubmed-article:17942747 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:17942747 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:17942747 | pubmed:pagination | 75-81 | lld:pubmed |
| pubmed-article:17942747 | pubmed:dateRevised | 2008-9-25 | lld:pubmed |
| pubmed-article:17942747 | pubmed:meshHeading | pubmed-meshheading:17942747... | lld:pubmed |
| pubmed-article:17942747 | pubmed:meshHeading | pubmed-meshheading:17942747... | lld:pubmed |
| pubmed-article:17942747 | pubmed:meshHeading | pubmed-meshheading:17942747... | lld:pubmed |
| pubmed-article:17942747 | pubmed:meshHeading | pubmed-meshheading:17942747... | lld:pubmed |
| pubmed-article:17942747 | pubmed:meshHeading | pubmed-meshheading:17942747... | lld:pubmed |
| pubmed-article:17942747 | pubmed:year | 2008 | lld:pubmed |
| pubmed-article:17942747 | pubmed:articleTitle | Identification of a novel ligand binding residue Arg38(1.35) in the human gonadotropin-releasing hormone receptor. | lld:pubmed |
| pubmed-article:17942747 | pubmed:affiliation | MRC Human Reproductive Sciences Unit, Centre for Reproductive Biology, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, United Kingdom. | lld:pubmed |
| pubmed-article:17942747 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:17942747 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
| entrez-gene:2798 | entrezgene:pubmed | pubmed-article:17942747 | lld:entrezgene |
| http://linkedlifedata.com/r... | entrezgene:pubmed | pubmed-article:17942747 | lld:entrezgene |
