Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0039483 (giant cell arteritis)
 3,204 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

While tandem repeats of the human centromere DNA pentamer sequence TGRAA form stable "self-complementary" [TGRAATGRAA]2 duplexes (R = G or A) containing the GA-bracketed unpaired purine stack motif, their phase-shifted variants NAATGNAATG (N = A, G, C, T) were found to exist in solution as an equilibrium mixture of a duplex containing the GA-bracketed unpaired stack motif and a hairpin containing a single-residue loop closed by a sheared G x A pair. The stability of the hairpin form relative to duplex form of GNA triplets was found to be GCA>GAA/GTA>>GGA, with the CAATGCAATG sequence mostly in the hairpin form and the GAATGGAATG sequence mostly in the [GAATGGAATG]2 duplex form. The chemical shifts of the H1' and H4' protons of the central N residue in GNA triplets were found to differ markedly in the duplex and hairpin forms and are diagnostic indicators of which conformation the oligonucleotide adopts. Comparison between the structures of the G x A-closed C loop motif and the G x A-bracketed unpaired G-stack [GGA]2 motif reveals remarkably similar stacking by the loop C residue and the intercalated G residue on the adjacent sheared G x A pair. The anomalous upfield chemical shifts of the H1' and H4' protons in [GGA]2 motifs and the H4' proton in GCA loops, and the different sugar conformations in these two motifs, can be explained by interstrand versus intrastrand stacking of the central (G or C) deoxyribose with the adenine base. Based on these studies, a DNA sequence GTGGAATGGAATGGAAC was designed and shown to form a duplex containing three [GGA]2 motifs, while its 9G-->9C analog GTGGAATGCAATGGAAC was found to adopt a stable hairpin containing a (GGA)2 motif in the stem and a G x A-closed single C-loop.
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PMID:On the relative ability of centromeric GNA triplets to form hairpins versus self-paired duplexes. 867 80

Hairpin loops belong to the most important structural motifs in folded nucleic acids. The d(GNA) sequence in DNA can form very stable trinucleotide hairpin loops depending, however, strongly on the closing base pair. Replica-exchange molecular dynamics (REMD) were employed to study hairpin folding of two DNA sequences, d(gcGCAgc) and d(cgGCAcg), with the same central loop motif but different closing base pairs starting from single-stranded structures. In both cases, conformations of the most populated conformational cluster at the lowest temperature showed close agreement with available experimental structures. For the loop sequence with the less stable G:C closing base pair, an alternative loop topology accumulated as second most populated conformational state indicating a possible loop structural heterogeneity. Comparative-free energy simulations on induced loop unfolding indicated higher stability of the loop with a C:G closing base pair by ~3 kcal mol(-1) (compared to a G:C closing base pair) in very good agreement with experiment. The comparative energetic analysis of sampled unfolded, intermediate and folded conformational states identified electrostatic and packing interactions as the main contributions to the closing base pair dependence of the d(GCA) loop stability.
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PMID:Role of the closing base pair for d(GCA) hairpin stability: free energy analysis and folding simulations. 2172 8