UMLS:C0162871 - FACTA Search

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Query: UMLS:C0162871 (abdominal aortic aneurysm)
8,664 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The reading of glutamine and lysine codons during protein synthesis in vitro has been investigated using an MS2-RNA-programed system derived from Escherichia coli. Under conditions when either glutaminyl-tRNA1Gln (s2UUG) or glutaminyl-tRNA2Gln (CUG) was the only source of glutamine for protein synthesis both tRNAs were able to read the glutamine codons CAA and CAG as indicated by the incorporation of labeled glutamine into the pertinent coat protein tryptic peptides. On the other hand, when the two glutamine tRNAs competed for the codon CAA the reading efficiency of the anticodon s2UUG, which reads the codon according to the wobble rules, was almost 40 times higher than that of the competing anticodon CUG, which reads the codon by "two out of three," i.e. it cannot form a regular base pair with the third codon position. In reading the codon CAG the anticodon CUG was approximately eight times more efficient than the anticodon s2UUG. The lysyl-tRNA1Lys (CUU) could not alone sustain any detectable coat protein synthesis in the MS2 system indicating that there was no significant reading of the lysine codon AAA. This conclusion is supported by the outcome of experiments where lysyl-tRNA1Lys (CUU) and lysyl-tRNA2Lys (s2UUU) competed for the codon AAA. The reading efficiency of the anticodon CUU was less than 1% of that of the competing s2UUU which represents the limit of resolution of our experimental system. When the two lysine tRNAs competed for the codon AAG the anticodon CUU was about four times more efficient than s2UUU. These results are discussed in the context of the two out of three hypothesis, which attempts to relate the frequency of such reading to the hydrogen bonding properties of the codon nucleotides.
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PMID:Codon reading and translational error. Reading of the glutamine and lysine codons during protein synthesis in vitro. 678 93

An analogue of Hoechst 33258, bearing a phenolic hydroxyl group in the meta rather than para position, was designed using molecular graphics to introduce hydrogen-bonding potentials between this OH group and the C = O group of cytosine-9 and the NH2 group of guanine-4', of the opposite strand of the B-DNA duplex, d(CGCGAATTCGCG)2. This derivative (meta-Hoechst) was synthesized in seven steps and characterized. Its binding to DNA was assessed by measurements of melting temperatures (Tm) and found to be similar in strength and AT preference to the parent Hoechst 33258 at this gross level. The AT preference of meta-Hoechst and Hoechst 33258 was probed further using hydroxyl radical footprinting on the tyrT DNA fragment, for which clear footprints were detected at AAT, AAA and ATAT runs, as for netropsin and distamycin. Hydroxyl radical footprinting was carried out on a trimer of CGCGAATTCGCG cloned into a longer DNA fragment, for which clear footprints for both Hoechst 33258 and meta-Hoechst were detected in regions with four or more contiguous AT base pairs. Three cell lines derived from haematological malignancies were more sensitive to both Hoechst 33258 and meta Hoechst than lines derived from solid tumours, but there was no significant difference between the activity of these two Hoechst derivatives.
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PMID:Synthesis, DNA binding, footprinting and in vitro antitumour studies of a meta-hydroxy analogue of Hoechst 33258. 757 88

In order to test the helical preference of short oligo-L-leucines, we crystallized the tripeptide L-leucyl-L-leucyl-L-leucine (LLL) and carried out x-ray diffraction studies of it (L-leucyl-L-leucyl-Lleucine)2. 3CH3OH. H2O, (C39H84N6O12), crystallized in the monoclinic system, space group P2(1), cell parameters: a = 12.031(2), b = 15.578(3), c = 14.087(2) A, alpha = 90 degrees, beta = 97.29(1) degrees, gamma = 90 degrees, V = 2618.6 A3, MW = 829.1, Dc = 1.051 g cm-3, R index of 0.057 for 4213 reflections (lambda CuK alpha = 1.5418 A) > 2 sigma. LLL takes up the beta-sheet rather than a helical conformation in the crystalline state. The three methanol molecules and the water molecule that constitute the solvent of crystallization form a network of hydrogen bonds to the LLL molecules and to one another. It is rather remarkable that though A and L have stronger helical preferences than G, neither AAA nor LLL form the crystalline helix but GAL does, indicating that the helical preferences depend on the sequence context. The residue L2 in molecule A and the residues L1 and L3 of molecule B do not show the preferred conformation for forming helices. Further, very remarkably, LLL exhibits a unique supersecondary feature of the protein folding topology, namely the twisted beta-sheet, whereas most short peptides show only the classical beta-sheet conformation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Crystal structure and a twisted beta-sheet conformation of the tripeptide L-leucyl-L-leucyl-L-leucine monohydrate trimethanol solvate: conformation analysis of tripeptides. 757 52

A non-discriminatory base analogue, or universal base, would be an invaluable component of oligonucleotide probes and primers for solving the design problems that arise as a result of the degeneracy of the genetic code, or when only fragmentary peptide sequence data are available. We have designed an alternative to previous universal nucleoside candidates, a new analogue, 1-(2'-deoxy-beta-D-ribofuranosyl)-3-nitropyrrole (designated M; Fig. 1), which maximizes stacking while minimizing hydrogen-bonding interactions without sterically disrupting a DNA duplex. Oligonucleotides containing M at several sites were used as primers for sequencing and the polymerase chain reaction. The sequencing primer d(5'-CGT AAM CAM AAM ACM AT-3') is as effective as the exact match d(5'-CGT AAT CAG AAA ACA AT-3'). It is also possible to sequence using a primer containing M at several contiguous positions, for example d(5'-CGT AAT MMM MMM MMM AT-3'). Melting curves show that duplexes formed on hybridization of the sequences d(5'-CCT TTT TMT TTT TGG-3') and d(5'-CCA AAA AXA AAA AGG-3'), where X is A, C, G or T, melted at a lower temperature than the corresponding duplexes containing only d(A.T) and d(C.G) base pairs, but showing little variation among different X bases (Tm range 3 degrees C).
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PMID:A universal nucleoside for use at ambiguous sites in DNA primers. 820 40

Mucins and other highly O-linked glycoproteins have been found to exist in random-coil conformations with peptide chain dimensions about 3-fold more expanded than found for deglycosylated mucins or denaturated proteins. We have examined the origin of the peptide chain expansion in mucins by stochastic dynamics simulations which include a treatment of solvation energy effects based on solvent-accessible surface area and polarizability [GB/SA; Still, C. W., et al. (1990) J. Am. Chem. Soc. 112, 6127]. The glycopeptides studied contained pairs of threonine residues (flanked by alanine residues) which were O-glycosylated by the di- and monooligosaccharide side chains alpha-NeuNAc(2-6)alpha-GalNAc and alpha-GalNAc. These glycopeptides serve as simple models for native and asialo ovine submaxillary mucin. Computer stochastic dynamic simulations show a significant decrease in end-to-end distance and radius of gyration (32% and 33%, respectively) upon complete removal of carbohydrate from the glycopeptide AAA(NeuNAc-(2-6)GalNAc)-T(NeuNAc(2-6)GalNAc)-TAAA. These changes are consistent with the extrapolations of the mucin chain dimension data to glycopeptides of this size. The simulations have identified two potentially strong peptide-carbohydrate hydrogen bonds that can influence the orientation of O-linked GalNAc. With two contiguous glycosylated sites, the lowest energy conformation obtained is characterized by a GalNAc amide proton hydrogen bond to the carbonyl of the peptide residue C-terminal to the site of glycosylation. This conformation differs from the glycopeptide conformations predicted for glycopeptides with single or widely spaced glycosylation sites. The results suggest that the experimentally determined mucin peptide chain dimensions can be fully accounted for by short-range (+/- 3 residue) intramolecular steric and hydrogen bond interactions resulting from the clustering of glycosylated residues.
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PMID:Structure and dynamics of mucin-like glycopeptides. Examination of peptide chain expansion and peptide-carbohydrate interactions by stochastic dynamics simulations. 844 22

We have studied the hydration and dynamics of RNA C2'-OH in a DNA. RNA hybrid chimeric duplex [d(CGC)r(aaa)d(TTTGCG)](2). Long-lived water molecules with correlation time tau(c) larger than 0.3 ns were found close to the RNA adenine H2 and H1' protons in the hybrid segment. A possible long-lived water molecule was also detected close to the methyl group of 7T in the RNA-DNA junction but not to the other two thymine bases (8T and 9T). This result correlates with the structural studies that only DNA residue 7T in the RNA-DNA junction adopts an O4'-endo sugar conformation (intermediate between B-form and A-form), while the other DNA residues including 3C in the DNA-RNA junction, adopt C1'-exo or C2'-endo conformations (in the B-form domain). Based on the NOE cross-peak patterns, we have found that RNA C2'-OH tends to orient toward the O3' direction, forming a possible hydrogen bond with the 3'-phosphate group. The exchange rates for RNA C2'-OH were found to be around 5-20 s(-1), compared to 26.7(+/-13.8) s(-1) reported previously for the other DNA.RNA hybrid duplex. This slow exchange rate may be due to the narrow minor groove width of [d(CGC)r(aaa)d(TTTGCG)](2), which may trap the water molecules and restrict the dynamic motion of hydroxyl protons. The distinct hydration patterns of the RNA adenine H2 and H1' protons and the DNA 7T methyl group in the hybrid segment, as well as the orientation and dynamics of the RNA C2'-OH protons, may provide a molecular basis for further understanding the structure and recognition of DNA.RNA hybrid and chimeric duplexes.
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PMID:Hydration of [d(CGC)r(aaa)d(TTTGCG)](2). 1065 92

Aryl acylamidase (EC 3.1.5.13; AAA) catalyzes the hydrolysis of p-nitroacetanilide (PNAA) via the standard three-step mechanism of serine hydrolases: binding of substrate (K(s)), acylation of active-site serine (k(acyl)), and hydrolytic deacylation (k(deacyl)). Key mechanistic findings that emerged from this study include that (1) AAA requires a deprotonated base with a pK(a) of 8.3 for expression of full activity toward PNAA. Limiting values of kinetic parameters at high pH are k(c) = 7 s(-1), K(m) = 20 microM, and k(c)/K(m) = 340 000 M(-1) s(-1). (2) At pH 10, where all the isotope effects were conducted, k(c) is equally rate-limited by k(acyl) and k(deacyl). (3) The following isotope effects were determined: (D)()2(O)(k(c)/K(m)) = 1.7 +/- 0.2, (D)()2(O)k(c) = 3.5 +/- 0.3, and (beta)(D)(k(c)/K(m)) = 0.83 +/- 0.04, (beta)(D)k(c) = 0.96 +/- 0.01. These values, together with proton inventories for k(c)/K(m) and k(c), suggest the following mechanism: (i) The initial binding of substrate to enzyme to form the Michaelis complex is accompanied by solvation changes that generate solvent deuterium isotope effects originating from hydrogen ion fractionation at multiple sites on the enzyme surface. (ii) From within the Michaelis complex, the active site serine attacks the carbonyl carbon of PNAA with general-base catalysis to form a substantially tetrahedral transition state enroute to the acyl-enzyme. (iii) Finally, deacylation occurs through a process involving a rate-limiting solvent isotope effect, generating conformational change of the acyl-enzyme that positions the carbonyl bond in a polarizing environment that is optimal for attack by water.
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PMID:Enzymatic hydrolysis of p-nitroacetanilide: mechanistic studies of the aryl acylamidase from Pseudomonas fluorescens. 1179 Jan 23

beta1- and beta2-adrenergic receptors (AR) regulate cardiac myocyte function through distinct signaling pathways. In addition to regulating cardiac rate and contractility, beta1AR and beta2AR may play different roles in the pathogenesis of heart failure. Studies on neonatal cardiac myocytes from beta1AR and beta2AR knockout mice suggest that subtype-specific signaling is determined by subtype-specific membrane targeting and trafficking. Stimulation of beta2ARs has a biphasic effect on contraction rate, with an initial increase followed by a sustained Gi-dependent decrease. Recent studies show that a PDZ domain-binding motif at the carboxyl terminus of human beta2AR interacts with ezrin-binding protein 50/sodium-hydrogen exchanger regulatory factor, a PDZ-domain-containing protein. The human beta2AR carboxyl terminus also binds to N-ethylmaleimide-sensitive factor, which does not contain a PDZ domain. We found that mutation of the three carboxyl-terminal amino acids in the mouse beta2AR (beta2AR-AAA) disrupts recycling of the receptor after agonist-induced internalization in cardiac myocytes. Nevertheless, stimulation of the beta2AR-AAA produced a greater contraction rate increase than that of the wild-type beta2AR. This enhanced stimulation of contraction rate can be attributed in part to the failure of the beta2AR-AAA to couple to Gi. We also observed that coupling of endogenous, wild-type beta2AR to Gi in beta1AR knockout myocytes is inhibited by treatment with a membrane-permeable peptide representing the beta2AR carboxyl terminus. These studies demonstrate that association of the carboxyl terminus of the beta2AR with ezrin-binding protein 50/sodium-hydrogen exchanger regulatory factor, N-ethylmaleimide-sensitive factor, or some related proteins dictates physiologic signaling specificity and trafficking in cardiac myocytes.
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PMID:The PDZ-binding motif of the beta2-adrenoceptor is essential for physiologic signaling and trafficking in cardiac myocytes. 1295 81

Like the beta-turns, which are characterized by a limiting distance between residues two positions apart (i, i+3), a distance criterion (involving residues at positions i and i+4) is used here to identify alpha-turns from a database of known protein structures. At least 15 classes of alpha-turns have been enumerated based on the location in the phi,psi space of the three central residues (i+1 to i+3)-one of the major being the class AAA, where the residues occupy the conventional helical backbone torsion angles. However, moving towards the C-terminal end of the turn, there is a shift in the phi,psi angles towards more negative phi, such that the electrostatic repulsion between two consecutive carbonyl oxygen atoms is reduced. Except for the last position (i+4), there is not much similarity in residue composition at different positions of hydrogen and non-hydrogen bonded AAA turns. The presence or absence of Pro at i+1 position of alpha- and beta-turns has a bearing on whether the turn is hydrogen-bonded or without a hydrogen bond. In the tertiary structure, alpha-turns are more likely to be found in beta-hairpin loops. The residue composition at the beginning of the hydrogen bonded AAA alpha-turn has similarity with type I beta-turn and N-terminal positions of helices, but the last position matches with the C-terminal capping position of helices, suggesting that the existence of a "helix cap signal" at i+4 position prevents alpha-turns from growing into helices. Our results also provide new insights into alpha-helix nucleation and folding.
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PMID:Expanded turn conformations: characterization and sequence-structure correspondence in alpha-turns with implications in helix folding. 1504 23

Novel triply hydrogen bonded suprastructures based on [M(tdpd)2(L)2]2- (H2tdpd=1,4,5,6-tetrahydro-5,6-dioxo-2,3-pyrazinedicarbonitrile, L=solvent) and melamine-analogous cations have been synthesized and characterized. The use of anions containing two AAA sets from [M(tdpd)2(L)2]2- together with cations containing one DDD set (A=hydrogen-bond acceptor, D=hydrogen-bond donor) leads to the formation of complementary triply hydrogen bonded modules in the solid state. In all cases, the building module is further extended via additional hydrogen-bonding interactions to produce a tape, and tapes are assembled into sheets. These results show that a hydrogen-bonded module consisting of different kinds of building blocks, one of which is a metal complex that includes hydrogen-bond acceptor sites and the other is a hydrogen-bond donor molecule, will be attractive for constructing metal-containing supramolecular systems by the self-assembly technique.
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PMID:Triple hydrogen bonds direct crystal engineering of metal-assembled complexes: the effect of a novel organic-inorganic module on supramolecular structure. 1613 Jan 58

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