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G J Quigley

Publications and source records attributed to G J Quigley.

At least 37 records · Page 2Linked to original sources

Structural basis for stabilization of Z-DNA by cobalt hexaammine and magnesium cations.

In the equilibrium between B-DNA and Z-DNA in poly(dC-dG), the [Co(NH3)6]3+ ion stabilizes the Z form 4 orders of magnitude more effectively than the Mg2+ ion. The structural basis of this difference is revealed in Z-DNA crystal structures of d(CpGpCpGpCpG) stabilized by either Na+/Mg2+ or Na+/Mg2+ plus [Co(NH3)6]3+. The crystals diffract X-rays to high resolution, and the structures were refined at 1.25 A. The [Co(NH3)6]3+ ion forms five hydrogen bonds onto the surface of Z-DNA, bonding to a guanine O6 and N7 as well as to a phosphate group in the ZII conformation. The Mg2+ ion binds through its hydration shell with up to three hydrogen bonds to guanine N7 and O6. Higher charge, specific fitting of more hydrogen bonds, and a more stable complex all contribute to the great effectiveness of [Co(NH3)6]3+ in stabilizing Z-DNA.

Cobalt↗

The molecular structure of a DNA-triostin A complex.

The molecular structure of triostin A, a cyclic octadepsipeptide antibiotic, has been solved complexed to a DNA double helical fragment with the sequence CGTACG (C, cytosine; G, guanine; T, thymine; A, adenine). The two planar quinoxaline rings of triostin A bis intercalate on the minor groove of the DNA double helix surrounding the CG base pairs at either end. The alanine residues form hydrogen bonds to the guanines. Base stacking in the DNA is perturbed, and the major binding interaction involves a large number of van der Waals contacts between the peptides and the nucleic acid. The adenine residues in the center are in the syn conformation and are paired to thymine through Hoogsteen base pairing.

Crystallization↗

Computer-aided nucleic acid secondary structure modeling incorporating enzymatic digestion data.

We present a computer-aided method for determining nucleic acid secondary structure. The method utilizes a program which has the capability to filter matrix diagonal data on the basis of diagonal length, stabilization energy, and chemical and enzymatic data. The program also allows the user to assign selected regions of the structure as uniquely single-stranded or paired, and to filter out "trade-off" structures on the basis of such pairing. In order to demonstrate the utility of the program we present a preliminary secondary structure for the 3' end of alfalfa mosaic virus RNA 4 (AMV-4 RNA). This structure is based on an analysis which includes the use of in vitro partial enzymatic digestion of the RNA.

Base Sequence↗

5'-Conformation of capped alfalfa mosaic virus ribonucleic acid 4 may reflect its independence of the cap structure or of cap-binding protein for efficient translation.

Most eukaryotic mRNAs are characterized by the presence of a 5'-terminal cap structure (m7GpppN), and removal of the cap or translation of capped mRNAs in the presence of cap analogues (m7G) results in most cases in a significant decrease in the translational efficiency of the mRNAs. One way of explaining the importance of the 5'-cap is that cap-binding proteins recognize the cap structure, destabilize the mRNA secondary structure, and thus allow the 40S ribosomal subunit to bind to the mRNA [Sonenberg, N., Guertin, D., Cleveland, D., & Trachsel, H. (1981) Cell (Cambridge, Mass.) 27, 563-572]. Our data and those of others indicate that the translational efficiency of alfalfa mosaic virus RNA 4 (AMV-4 RNA), a naturally capped RNA, is not affected significantly by cap analogues or by removal of the cap. In order to examine the potential relationship between the function of the cap structure and secondary structure at the 5'-mRNA terminus, partial enzymatic digestion of capped AMV-4 RNA with single strand specific and double strand specific nucleases has been performed, and the experimental data have been compared with computer-generated models of AMV-4 secondary structure. In addition, the in vitro translatability of AMV-4 has been examined as a function of increasing potassium concentration, conditions that are likely to increase mRNA secondary structure. The nuclease-digestion results demonstrate that under native ionic conditions, the 5'-terminus of AMV-4 RNA is predominantly single stranded, although computer modeling and double-strand nuclease digestions indicate that the 5'-terminus can form weak base pairs with internal regions of the molecule.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗

Transvaginal retropubic urethropexy. The "revised Pereyra procedure": report of 50 cases.

Fifty patients with uterovaginal prolapse were treated by transvaginal retropubic urethropexy to correct the anatomic defect of their urethrovesical axis. Urodynamic studies were routine in the preoperative assessment. Forty patients had anatomic sphincteric incontinence. Forty-one (82% of the 50 patients treated were totally continent of urine after a follow-up of 12 to 36 months. The complications and results of this procedure are comparable to those of other abdominal retropubic procedures for urinary incontinence. The suggestion is made that, in the surgical management of symptomatic uterovaginal prolapse, this procedure, which can be easily performed in conjunction with any vaginal operation, may be an alternative to a combined vaginal and abdominal approach.

Adult↗

Left-handed double helical DNA: variations in the backbone conformation.

Four different crystals of d(CpGpCpGpCpG) have been solved by x-ray diffraction analysis and all form similar left-handed double helical Z-DNA molecules in the crystal lattice. Two different conformations are observed for the phosphates in the GpC sequences, as the phosphates are found either facing the helical groove or rotated away from it. The latter conformation is often found when hydrated magnesium ions are complexed to a phosphate oxygen atom. These different conformations may be used when right-handed B-DNA joins left-handed Z-DNA. Atomic coordinates and torsion angles are presented for both types of Z-DNA.

DNA↗

Molecular structure of an anticancer drug-DNA complex: daunomycin plus d(CpGpTpApCpG).

The structure of the crystalline daunomycin-d(CpGpTpApCpG) complex has been solved by x-ray diffraction analysis. The DNA forms a six-base-pair right-handed double helix with two daunomycin molecules intercalated in the d(CpG) sequences. The daunomycin aglycone chromophore is oriented at right angles to the long dimension of the DNA base pairs and the cyclohexene ring rests in the minor groove. Substituents on this ring have hydrogen bonding interactions to the base pairs above and below the intercalation site. These appear to be specific for anthracycline antibiotics. The amino sugar lies in the minor groove of the double helix without bonding to the DNA. The DNA double helix is distorted in a novel manner in accommodating the drug.

Daunorubicin↗

The tetramer d(CpGpCpG) crystallizes as a left-handed double helix.

The structure of the tetramer d(CpGpCpG) has been solved by x-ray analysis in two different crystal forms with and without spermine cations. The molecules crystallize in hexagonal unit cells and they form a left-handed double helix of Z-DNA similar to that previously reported for the hexamer d(CpGpCpGpCpG). In the crystal lattice the molecules stack together to form a virtually continuous left-handed double helix in which every fourth phosphate group is missing. The stacking of bases upon each other is similar to that seen in the hexamer. However, the base pairs have a slightly different orientation in that the cytosine residues are slightly removed from the axis of the molecule compared to the position they occupy in the hexamer. The structures are similar in two crystal forms with and without spermine cations.

Base Sequence↗

Atomic resolution analysis of a 2:1 complex of CpG and acridine orange.

Cytidylyl-3', 5'-guanosine and acridine orange crystallize in a highly-ordered triclinic lattice which diffracts X-rays to 0.85 angstrom resolution. The crystal structure has been solved and refined to a residual factor of 9.5%. The two dinucleoside phosphate molecules form an antiparallel double helix with the acridine orange intercalated between them. The two base pairs of the double helical fragment have a twist angle of 10 degrees and it is found to have a C3' endo-(3', 5')-C2' endo mixed sugar puckering along the nucleotide backbone as has been observed for other simple intercalator complexes. Twenty-five water molecules have been located in the lattice together with a sodium ion. The intercalator double helical fragments form sheets which are held together by van der Waals interactions in one direction and hydrogen bonding interactions in the other. The crystal lattice contains aqueous channels in which sixteen water molecules are hydrogen bonded to the nucleotide, none to the intercalator, five water molecules are coordinated about the sodium ion and four water molecules bind solely to other water molecules. The bases in the base pairs have a dihedral angle of 7 to 8 degrees between them.

Acridine Orange↗

Structural analysis of spermine and magnesium ion binding to yeast phenylalanine transfer RNA.

Refinement of the diffraction data at 2.5-A resolution from orthorhombic crystals of yeast tRNAPhe has proceeded to the point where spermine and magnesium ions can be located in the difference electron density map. Two spermine molecules are found: one is located in the major groove at one end of the anticodon stem; the other is near the variable loop and curls around phosphate 10 in a region where the polynucleotide chain takes a sharp turn. Four distinct magnesium ions have been identified: one in the anticodon loop, two in the D loop, and one coordinated with phosphates 8, 9, 11, and 12, where the polynucleotide chain is coiled. The conformation of the anticodon stem and loop is stabilized by the cations at the end of the molecule. The positions of these ions may be related to aspects of the biological activity of tRNA. The spermine and magnesium ions appear to be important in maintaining the overall folding of the tRNA molecule.

Anticodon↗

Structural domains of transfer RNA molecules.

In this article, we have described various detailed features of the conformation of yeast tRNA(Phe) revealed by recent refinement analysis of x-ray diffraction data at 2.5 A resolution. The gross features of the molecule observed in the unrefined version have been largely confirmed and a number of new features found. The unique role of the ribose 2' hydroxyl groups in maintaining a series of nonhelical conformations in this RNA molecule has become apparent. Many of these features are a direct consequence of the geometry of the ribose phosphate backbone of RNA molecules, and these may also be found in structured regions of other RNA species as well. Special attention has been directed toward two conformational motifs revealed by this analysis. These include the striking similarity between the TpsiC and anticodon hairpin turns in the polynucleotide chain, which are stabilized by the participation of uridine in the U turn. In addition, there is frequent occurrence of an arch conformation in the polynucleotide chian which is stabilized by hydrogen bonds from 2' hydroxyl residues to phosphate groups across the base of the arch. The importance of the 2' hydroxyl interactions in defining tertiary structure is illustrated by the fact that, in the nonhelical regions, almost half of the ribose residues are involved in O2' hydrogen-bonding interactions which stabilize the conformation of the molecule.

Anticodon↗

Hydrogen bonding in yeast phenylalanine transfer RNA.

Further analysis of the three-dimensional electron density map of yeast phenylalanine tRNA is presented. Attention is focused on the several types of unique hydrogen bonding that are found in the molecule and a number of sections of the electron density map are presented. These sections are compared with an electron density map of a dinucleoside phosphate. The bases in the helical stem regions are all involved in Watson-Crick hydrogen bonding interactions with the exception of the guanine-uracil base pair. Several additional tertiary hydrogen bonding interactions are described.

Anticodon↗

Yeast phenylalanine transfer RNA: atomic coordinates and torsion angles.

The atomic coordinates of yeast phenylalanine transfer RNA (tRNA) as well as the torsion angles of the polynucleotide chain are presented as derived from an x-ray diffraction analysis of orthorhombic crystals. A comparison is made between the coordinates obtained from analysis of monoclinic crystals of the same material. It is concluded that the molecule has substantially the same form in the orthorhombic and the monoclinic lattices, except for differences found between residues at the 3' end of the polynucleotides chain. A number of observations are made concerning hydrogen bonding interactions which may account for many of the residues conserved in all tRNA sequences.

Nucleic Acid Conformation↗