Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01350 (gastrin)
 9,683 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report below on the NMR structural characterization of the complex between AMP and a 40-mer RNA aptamer in aqueous solution. Resonance assignments are based on multinuclear multidimensional NMR studies on complexes uniformly 13C, 15N-labeled with either AMP or the RNA aptamer. AMP binds to an internal loop (labeled G7-G8-A9-A10-G11-A12-A13-A14-C15-U16-G17) and bulge (G34 positioned opposite the internal loop) segment in the RNA aptamer, and our NMR study provides insights into features of the RNA folding topology and the molecular recognition events in the AMP binding pocket on the RNA. Specifically, the helical stems are extended by G-G mismatch formation from either direction into the internal loop/bulge segment of the RNA aptamer on complex formation. The internal loop adopts a unique fold with the purine ring of AMP intercalated between A10 and G11 in the complex. The G8-A9-A10-AMP segment adopts certain stacking features in common with a GNRA turn and is closed by the G7.G11 mismatch pair. The purine rings of A12 and G34 (syn) are stacked on each other and participate in stablizing the AMP intercalation site. A large number of intermolecular NOEs have been identified between the AMP ligand and the G8, A10, G11, G17, U18, and G34 residues on the RNA aptamer in the complex. The Watson-Crick edge of the AMP is oriented toward the exocyclic amino group of G8, suggestive of a hydrogen-bonding alignment between G8 and AMP in the complex. The AMP sugar ring is positioned in the minor groove of the rightward helical stem centered about the G17.G34 mismatch and U18.A33 Watson-Crick pairs. The AMP binds to one face of the folded internal loop/bulge segment of the RNA aptamer while the opposite face is capped by a stacked alignment of the A13-A14-C15-U16 segment located toward the 3'-end of the internal loop segment. Globally, the two helical stems of the RNA aptamer are aligned approximately orthogonal to each other with tertiary interactions centered about the internal loop/bulge segment generating the AMP binding site on the RNA.
 ...
PMID:RNA folding topology and intermolecular contacts in the AMP-RNA aptamer complex. 885 64

Research has widely supported the efficacy of screening for colorectal cancer in reducing mortality. A blood-based assay potentially represents a more accessible early detection tool for the identification of solid tumor cells originating from a primary tumor site in the body. We demonstrate a relatively easy and highly reproducible technique for the detection of mRNA expression of genes as markers of malignancy in blood samples of patients with colon cancer. The present study aims to identify a set of specific mRNAs expressed in epithelial cells but not in blood cells, which may be useful as markers for early detection of circulating colon cancer cells by a simple, qualitative RT-PCR assay following semi-automated RNA extraction from peripheral blood samples. Our approach includes a systematic search for candidate markers using digital differential display, search on UniGene colon EST libraries and analysis of published data on colon cancer gene expression. A final list included the following genes: bone morphogenetic protein 4 (BMP4), cyclin D (CycD), family with sequence similarity 3, member D (FAM3D), gastrin (GAS), glycoprotein A33 transmembrane (GPA33), glutathione peroxidase 2 gastrointestinal (GPX2), galactoside-binding, soluble, 4 (galectin 4) (LGALS4), non-SMC, structural maintenance of chromosomes, element 1 protein (NSE1), tumor-associated calcium signal transducer 1 (TACSTD1), telomerase reverse transcriptase (hTERT), trefoil factor 3 intestinal (TFF3), transmembrane 4 superfamily member 3 (TM4SF3), UDP glycosyltransferase 1 family, polypeptide A9 (UGT1A9), villin 1 (VIL1), and the novel gene FLJ20127. The mRNA expression of these genes was evaluated in a pool of 16 samples from subjects diagnosed with colon cancer and from 16 normal-controls. We observed expression in 13 of the 15 investigated genes from the blood samples of the vast majority of patients considered, but also in a certain percentage of the controls (from 14.3 to 100%). This finding confirms that the extreme sensitivity of RT-PCR is able to detect minimal amounts of mRNA expressed in a non tissue-specific manner ('illegitimate transcription'). On the contrary, NSE1 and GAS mRNAs were not detected either in patient or in control blood samples; however, they were abundantly expressed in normal and cancerous colon mucosa, encouraging further search for useful markers able to detect epithelial cells in peripheral blood.
 ...
PMID:Search for epithelial-specific mRNAs in peripheral blood of patients with colon cancer by RT-PCR. 1537 55