Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “structure”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 55 records · Page 3Linked to original sources
PubMed1994

Nucleic acid structure analysis. Mathematics for local Cartesian and helical structure parameters that are truly comparable between structures.

Analyzing nucleic acid structures in a comparable manner has become increasingly important as the number of solved structures has increased. This paper presents the concepts, mathematics, theorems, and proofs that form the basis of a new program to analyze three-dimensional DNA and RNA structures. The approach taken here provides numerical data in accordance with guidelines set at a 1988 EMBO workshop. Mathematical definitions are provided for all local structural parameters described in the guidelines. The definitions satisfy the guideline requirements while preserving the original physical intuition of the parameters. In particular, the rotational parameters are true rotations based on a simple physical model (net rotation at constant angular velocity), not Euler angles or angles between vectors and planes as is the case with other approaches. As a result, the mathematical definitions are symmetrical with the property that a 5 degrees tilt is the same as a 5 degrees roll and a 5 degrees twist, except that the rotations take place about different axes. In other approaches, a 5 degrees tilt can mean a different amount of net rotation than a 5 degrees roll or a 5 degrees twist. A second unique feature of the mathematics is that it explicitly incorporates the concept of a pivot point, which is the point about which a base in a base-pair rotates as it buckles, propeller twists, and opens. Pivot points enable one to model the physical motion of bases more accurately. As a result, they greatly reduce and/or eliminate the statistical correlations between rotational and translational parameters that arise as mathematically induced artifacts in other approaches. This paper, together with the statistical analysis in the companion paper for determining the locations of the pivot points, provides everything needed to understand the output of the program as it relates to individual structures.

Base Composition↗
PubMed1995

Structure of deoxyhaemoglobin of the antarctic fish Pagothenia bernacchii with an analysis of the structural basis of the root effect by comparison of the liganded and unliganded haemoglobin structures.

We have determined the structure of deoxyhaemoglobin from the antarctic fish Pagothenia bernacchii at pH 6.2 to a resolution of 2.2 A with X-ray data from a twinned crystal deconvoluted so as to approximate data from a single crystal. The R-factor between the (twinned) model and the observed data is 16% for reflections used in refinement and 22% for reflections not used in refinement. The T (deoxy) structure was compared with the R (liganded) structure at pH 8.0 in an attempt to understand the structural basis of the greater affinity for hydrogen ions of T, relative to R, that comprises the Root effect. Up to half of the effect can be attributed to interaction of the residues Asp95 (G1)alpha and Asp101 (G3)beta: in R the residues are far apart and their carboxyl groups are unprotonated, but the shift at the alpha 1 beta 2 interface that accompanies the R to T transition brings them so close that they appear to share a proton between them. The proximity of Asp99 (G1)beta may contribute to the required raising of the pKa values of the other two Asp residues. These and neighbouring residues are sufficiently conserved in the haemoglobins of trout (component IV), carp and bluefin tuna, all of which exhibit the Root effect, for the same mechanism to apply. However, the environment is equally conserved in haemoglobins of Trematomus newnesi (major component) and trout (component I), which do not exhibit the Root effect, so that the structural factors controlling the Asp-Asp interaction remain unclear. No other residue appears to undergo an R to T change in the immediate neighbourhoods that could account for any significant portion of the Root effect, so at least half of the effect must result either from long-range electrostatic interactions or from a large number of local interactions.

Animals↗
PubMed1991

Modeling RNA secondary structures. I. Mathematical structural model for predicting RNA secondary structures.

A mathematical model for analyzing the secondary structures of RNA is developed that is based on the connection matrix associated with the planar p-h graph. The classification of the elementary structures allows the introduction of the basis of structural space from which to build the global secondary structure. All admissible solutions belong to the configuration space and can be obtained directly from its basis.

Algorithms↗
PubMed2003

Potential for dramatic improvement in sequence alignment against structures of remote homologous proteins by extracting structural information from multiple structure alignment.

A novel method has been developed for acquiring the correct alignment of a query sequence against remotely homologous proteins by extracting structural information from profiles of multiple structure alignment. A systematic search algorithm combined with a group of score functions based on sequence information and structural information has been introduced in this procedure. A limited number of top solutions (15,000) with high scores were selected as candidates for further examination. On a test-set comprising 301 proteins from 75 protein families with sequence identity less than 30%, the proportion of proteins with completely correct alignment as first candidate was improved to 39.8% by our method, whereas the typical performance of existing sequence-based alignment methods was only between 16.1% and 22.7%. Furthermore, multiple candidates for possible alignment were provided in our approach, which dramatically increased the possibility of finding correct alignment, such that completely correct alignments were found amongst the top-ranked 1000 candidates in 88.3% of the proteins. With the assistance of a sequence database, completely correct alignment solutions were achieved amongst the top 1000 candidates in 94.3% of the proteins. From such a limited number of candidates, it would become possible to identify more correct alignment using a more time-consuming but more powerful method with more detailed structural information, such as side-chain packing and energy minimization, etc. The results indicate that the novel alignment strategy could be helpful for extending the application of highly reliable methods for fold identification and homology modeling to a huge number of homologous proteins of low sequence similarity. Details of the methods, together with the results and implications for future development are presented.

Algorithms↗
PubMed1985

The effect of salt extraction on the structure of transcriptionally active genes; evidence for a DNAseI-sensitive structure which could be dependent on chromatin structure at levels higher than the 30 nm fibre.

The procedure developed by Lawson and Cole (Biochemistry, 1979, 18 2161-2166) for removing lysine-rich histones from nuclei at low pH also quantitatively extracts proteins HMG14 and 17. The effect of this low pH extraction on the DNAseI-sensitive structures of active genes in avian red blood cells has been investigated. No major perturbation of a developmentally regulated DNAseI hypersensitive site in the beta-globin domain and at the 5' end of the alpha D gene was seen. The overall DNAseI-sensitive conformation of the beta A-globin gene (relative to the ovalbumin gene) is minimally affected by pH3 salt extraction, but there is some loss of sensitivity of the alpha D gene. Removal of HMG proteins at neutral pH had no effect on the sensitivity of active genes in erythroid or fibroblast nuclei. These results, together with those carried out on DNAseI sensitivity and HMG binding to monomer nucleosomes, indicate that there is a major structural feature of active genes responsible for DNAseI-sensitivity which is independent of HMG proteins or nucleosome core particle structure but may be dependent on higher order chromatin structures.

Animals↗
PubMed2002

Structure-activity relationships of a novel class of endothelin-A receptor antagonists and discovery of potent and selective receptor antagonist, 2-(benzo[1,3]dioxol-5-yl)-6-isopropyloxy-4-(4-methoxyphenyl)-2H-chromene-3-carboxylic acid (S-1255). 1. Study on structure-activity relationships and basic structure crucial for ET(A) antagonism.

A novel series of endothelin-A (ET(A)) selective receptor antagonists having a 2H-chromene skeleton are described. A lead compound, 2-(benzo[1,3]dioxol-5-yl)-2H-chromene-3-carboxylic acid (3), was found by modifications of our own angiotensin II antagonist. A structure-activity relationship (SAR) study of 3 reveals that the structural requirements essential for potent and selective ET(A) receptor binding affinity are the m,p-methylenedioxyphenyl, carboxyl, and isopropoxy groups at the 2-, 3-, and 6-positions, respectively, on the (R)-2H-chromene skeleton. The substituent at the 4-position is also important for improving the activity, and various hydrophobic functional groups of 6-9 A such as liner, branched, and cyclic aliphatic groups, unsubstituted and substituted aryl groups, and even halogen atoms were acceptable. These results suggest that (R)-2-(benzo[1,3]dioxol-5-yl)-6-isopropoxy-2H-chromene-3-carboxylic acid, formula 108, is the crucial basic structure to be recognized by the ET(A) receptor. The most potent compound is (R)-48 (S-1255), which binds to the ET(A) receptor with an IC(50) value of 0.19 nM and is 630-fold selective for the ET(A) receptor than for the ET(B) receptor. This compound has 55% oral bioavailability in rats. On the basis of the SAR, the roles of each substituent in the receptor binding are discussed.

Animals↗
PubMed1997

[PAF-antagonists with lipid structure. 6. Alkylpropandiol lipids with acyl- and ether- structures at the C-3 position and heterocyclic head groups; synthesis, characterization and structure-activity relationship].

A series of 14 PAF-analogues with simple lipid structure and heterocyclic head groups were synthesized, and the PAF-inhibitory potencies on human blood platelets was evaluated in vitro. Structure-activity relationships revealed that the PAF-antagonist activity is strongly influenced by the distance between position C-3 of the backbone and onium center and the structure of the heterocyclus. The best activity showed the 3,5-dimethylpyridinium derivative with a distance of 5 methylene groups (IC50 = 0.8 mumol/l).

Blood Platelets↗
PubMed1987

Nuclear magnetic resonance study of the solution structure of alpha 1-purothionin. Sequential resonance assignment, secondary structure and low resolution tertiary structure.

The solution structure of the 45-residue plant protein, alpha 1-purothionin, is investigated by nuclear magnetic resonance (n.m.r.) spectroscopy. Using a combination of two-dimensional n.m.r. techniques to demonstrate through-bond and through-space (less than 5 A) connectivities, the 1H n.m.r. spectrum of alpha 1-purothionin is assigned in a sequential manner. The secondary structure elements are then delineated on the basis of a qualitative interpretation of short-range nuclear Overhauser effects (NOE) involving the NH, C alpha H and C beta H protons. There are two helices extending from residues 10 to 19 and 23 to 28, two short beta-strands from residues 3 to 5 and 31 to 34 which form a mini anti-parallel beta-sheet, and five turns. In addition, a number of long-range NOE connectivities are assigned and a low resolution tertiary structure is proposed.

Amino Acid Sequence↗
PubMed1998

Genetic pattern, histological structure, and cellular phenotype in early and advanced gastric cancers: evidence for structure-related genetic subsets and for loss of glandular structure during progression of some tumors.

Gastric cancer shows remarkable heterogeneity in histological pattern, cellular phenotype, and genotype. Tumor subsets identified by varying procedures have shown limited reciprocal correlation and have failed to provide a sound rationale for the characterization and classification of all tumors. Based on a case series of 130 gastric cancers that covered both early (70 cases) and advanced (60 cases) stages and that represented most histological types and structural patterns, this study investigated (1) microsatellite instability and p53 gene mutation by means of PCR-based molecular techniques and (2) p53 protein accumulation or tumor cell immunophenotype by means of immunoperoxidase procedures. It was found that microsatellite instability and p53 gene mutation involve two distinct subsets of both early and advanced-stage glandular (intestinal) cancer, and that, contrastingly, they leave purely diffuse cancers unaffected. Mixed cancers, namely, those in which glandular admixed with diffuse growths, showed scarce microsatellite instability at all stages, whereas prominent p53 gene mutation and p53 protein accumulation was limited to the advanced stage alone. No significant correlation was found between tumor cell immunophenotype and either genotype or histotype, although some correlation with particular structural patterns was detected. Comparison of intramucosal with invasive growths within any given tumor suggested that invasive cancers with diffuse-type growth arise in part from mucosal cancers of glandular or mixed structure through progressive loss of intercellular junctional systems. It is concluded that at least two genetically distinct subsets of glandular cancer, one with microsatellite instability and the other with p53 lesions, should be separated both from purely diffuse cancer and, at least in the advanced stage, from mixed cancer. Available evidence suggests distinct clinicopathologic profiles for such tumor entities.

Aged↗
PubMed2001

Oxamato-bridged trinuclear Ni(II)Cu(II)Ni(II) complexes with irregular spin state structures and a binuclear Ni(II)Cu(II) complex with an unusual supramolecular structure: crystal structure and magnetic properties.

Four oxamato-bridged heterotrinuclear Ni(II)Cu(II)Ni(II) complexes of formula ([Ni(bispictn)](2)Cu(pba))(ClO(4))(2).2.5H(2)O (1), ([Ni(bispictn)](2)Cu(pbaOH))(ClO(4))(2).H(2)O (2), ([Ni(cth)](2)Cu(pba))(ClO(4))(2) (3), and ([Ni(cth)](2)Cu(opba))(ClO(4))(2).H(2)O (4) and a binuclear Ni(II)Cu(II) complex of formula [Cu(opba)Ni(cth)].CH(3)OH (5) have been synthesized and characterized by means of elemental analysis, IR, ESR, and electronic spectra, where pba = 1,3-propylenebis(oxamato), pbaOH = 2-hydroxyl-1,3-propylenebis(oxamato), opba = o-phenylenebis(oxamato), bispictn = N,N'-bis(2-pyridylmethyl)-1,3-propanediamine, and cth = rac-5,7,7,12,14,14-hexamethyl-1,4,8,11-tetraazacyclotetradecane. The crystal structures of 1, 3, and 5 have been determined. The structures of complexes 1 and 3 consist of trinuclear cations and perchlorate anions, and that of 5 consists of neutral binuclear molecules which are connected by hydrogen bonds and pi-pi interactions to produce a unique supramolecular "double" sheet. In the three complexes, the copper atom in a square-planar or axially elongated octahedral environment and the nickel atom in a distorted octahedral environment are bridged by the oxamato groups, with Cu.Ni separations between 5.29 and 5.33 A. The magnetic properties of all five complexes have been investigated. The chi(M)T versus T plots for 1-4 exhibit the minimum characteristic of antiferromagnetically coupled NiCuNi species with an irregular spin state structure and a spin-quartet ground state. The chi(M)T versus T plot for 5 is typical of an antiferromagnetically coupled NiCu pair with a spin-doublet ground state. The Ni(II)-Cu(II) isotropic interaction parameters for the five complexes were evaluated and are between 102 and 108 cm(-)(1) (H = -JS(Cu).S(Ni)).

Journal Article↗
PubMed1984

The structure of the human tissue-type plasminogen activator gene: correlation of intron and exon structures to functional and structural domains.

A genomic clone carrying the human tissue-type plasminogen activator (t-PA) gene was isolated from a cosmid library, and the gene structure was elucidated by restriction mapping, Southern blotting, and DNA sequencing. The cosmid contained all the coding parts of the mRNA, except for the first 58 bases in the 5' end of the mRNA, and had a total length of greater than 20 kilobases. It was separated into at least 14 exons by at least 13 introns, and the exons seemed to code for structural or functional domains. Thus, the signal peptide, the propeptide, and the domains of the heavy chain, including the regions homologous to growth factors, and to the "finger" structure of fibronectin, are all encoded by separate exons. In addition, the two kringle regions of t-PA were both coded for by two exons and were cleaved by introns at identical positions. The region coding for the light chain, comprising the serine protease part of the molecule was split by four introns, revealing a gene organization similar to other serine proteases.

Amino Acid Sequence↗
PubMed1995

Antihyperglycemic N-sulfonyl-1a,2,6,6a-tetrahydro-1H,4H- [1,3]dioxepino[5,6-b]azirines: synthesis, X-ray structure analysis, conformational behavior, quantitative structure-property relationships, and quantitative structure-activity relationships.

A series of 1-sulfonyl-1a,2,6,6a-tetrahydro-1H,4H- [1,3]dioxepino[5,6-b]azirines, 4, has been synthesized and evaluated for its effects on blood glucose-decreasing activity. These derivatives were prepared from 4,7-dihydro-1,3-dioxepins 1 via vic(acylamino)halogenodioxepanes 2 and dioxepinoazirines 3. Quantitative structure--property relationship and quantitative structure--activity relationship models, based on X-ray and molecular mechanics analyses, to our knowledge the first in the field of antihyperglycemics, were developed. They allow the prediction of properties (RP-HPLC attention times) and activities (hypoglycemic activity ratio) by the Connolly's molecular surface areas. The lead compound in these models, sulfonyldioxepinoazirine 4i, expressed superior antihyperglycemic activity in comparison to metformin in alloxanized mice, irrespective of route of application. It significantly reduced blood glucose levels in glucose-primed mice, but it did not cause a dose dependent decrease of blood glucose level in healthy (nondiabetic, control) animals.

Animals↗
PubMedDate not supplied

Structure-activity relations of polyfunctional diterpenes of the daphnane type. I. Revised structure for resiniferatoxin and structure-activity relations of resiniferonol and some of its esters.

Base catalyzed transesterifications of resiniferatoxin afforded the 9, 13, 14-orthophenylacetate (III), as well as (4-hydroxy-3-methyoxyphenyl) acetic acid methyl ester (II). Reesterification of III with homovanillic acid showed that the previously proposed structure for resiniferatoxin has to be revised to resiniferonol-9, 13, 14-orthophenylacetate-20-(4-hydroxy-3-methoxyphenyl) acetate (I). From III, different 20 esters (I, IV-IX) were prepared. The orthophenylacetate III was cleaved by Acidic hydrolysis to yield the 14-phenylacetate X. Subsequent alkaline transesterifications of X afforded the parent alcohol resiniferonol (XI), Starting from XI, the 14, 20-diesters XII and XV and the 9, 13, 20-diesters xii and XV and the 9, 13, 14-orthoesters XIII, XIV, XVI, XVII and XVIII were obtained. All esters were tested for irritant activity on the mouse ear. Some aspects of structure-activity relations of irritancy of resiniferonol esters are established and discussed.

Animals↗
PubMed1988

Structural analysis of recombinant soluble human interleukin-2 receptor. Primary structure, assignment of disulfide bonds and core IL-2 binding structure.

A purified soluble and functional form of recombinant human interleukin-2 receptor, engineered and expressed in Chinese hamster ovary cells, was structurally characterized. The primary sequence of this 224 amino acid recombinant protein which lacks most of the carboxy-terminal transmembrane and cytoplasmic portions of the intact protein was established by sequence analyses. The disulfide bonds were assigned by comparative peptide mapping of the reduced and non-reduced peptide digests. As in the case of natural interleukin-2 receptor they occur between cysteines 3-147, 46-104, 131-163, and 28/30-59/61. Based on assignment of the disulfide bonds, a structural model of the interleukin-2 receptor for interleukin-2 binding is proposed.

Amino Acid Sequence↗
PubMed1987

The secondary structure of myelin P2 protein derived by secondary structure prediction methods, circular dichroism, and 400-MHz 1H-NMR spectroscopy: implications for tertiary structure.

The various methods used to study the secondary and tertiary structure of myelin P2 protein, and one of its peptides (CN1), in aqueous solution, indicate that the native protein contains a significant fraction of alpha-helix, suggesting that the current prediction of an all-beta tertiary structure requires revision.

Amino Acid Sequence↗
PubMed2000

Structural characterization and formation mechanism of sitting-atop (SAT) complexes of 5,10,15,20-tetraphenylporphyrin with divalent metal ions. Structure of the Cu(II)-SAT complex as determined by fluorescent extended X-ray absorption fine structure.

The UV-vis absorption spectra and the formation kinetics of sitting-atop (SAT) complexes (M(H2tpp)2+) of 5,10,15,20-tetraphenylporphyrin (H2tpp) with a series of divalent metal ions (M2+ = Mn2+, Fe2+, Co2+, Ni2+, Cu2+, and Zn2+) in acetonitrile have been investigated. The structural characteristics of the SAT complexes for a series of M2+ ions are discussed on the basis of the UV-vis absorption spectra. The structure parameters around Cu2+ in the Cu(II)-SAT complex were determined by a fluorescent EXAFS method: the coordination number is 6 with three kinds of Cu-N interactions having bond lengths of 2.05, 1.98, and 2.32 A for pyrrolenine nitrogens of H2tpp, acetonitrile nitrogens at equatorial sites, and acetonitrile nitrogens at axial sites, respectively. The rate constants at 25 degrees C for the formation of the SAT complex in acetonitrile are as follows: kf/mol-1 kg s-1 = 3.4 x 10(2) for Mn2+, 0.18 for Co2+, 1.6 x 10(-3) for Ni2+, and 61 for Zn2+. The finding that the variation trends in the rate constants for a series of M2+ ions for the SAT complex formation and the solvent exchange reaction in various solvents are very similar indicates that the rate-determining step for the SAT complex formation is the interchange between the coordinating nitrogen of a bound acetonitrile and the pyrrolenine nitrogen of H2tpp. The fact that the values of kf are smaller by 4-6 orders of magnitude in comparison with those of the solvent exchange suggests that there is a large energetic loss due to the fast preequilibria prior to the rate-determining step, such as deformation of a porphyrin ring and outer-sphere encounter formation due to an electrostatic interaction between M2+ and the local negative charge on the pyrrolenine nitrogens. We observed the subsequent formation of the corresponding metalloporphyrins by deprotonation of the SAT complex and oxidation of the M2+ center, of which the dynamic behavior was significantly different for the different M2+ ions.

Journal Article↗
PubMed1996

A(15)Tl(27) (A = Rb, Cs): A Structural Type Containing Both Isolated Clusters and Condensed Layers Based on the Tl(11) Fragment. Syntheses, Structure, Properties, and Band Structure.

The isomorphous title compounds (and the ordered substitutional Rb(14)CsTl(27)) are obtained directly from reactions of the elements in sealed Ta below approximately 330 degrees C. Refinements of single-crystal data for the three established a structure with alternate layers of isolated pentacapped trigonal prismatic Tl(11)(7)(-) (D(3)(h)()) ions and condensed [Tl(16)(8-)] networks that are separated by cations. The condensed layer consists of Tl(11) units that share prismatic edges and are interbridged through waist-capping atoms (Tl(6/2)Tl(3)Tl(2)). (Rb(15)Tl(27): P&sixmacr;2m, Z = 1, a = 10.3248(6) Å, c = 17.558(2) Å.) The rubidium phase is a poor metal (rho(293) approximately 34 &mgr;Omega.cm) and is Pauli-paramagnetic. Extended Hückel band calculations indicate partially filled bands and a non-zero DOS at E(F), consistent with the observed metallic behavior, although appropriate cation tuning or modest anion doping should provide a Zintl phase. The band structure and COOP curves are also used to rationalize the distortion of the Tl(11) unit on condensation and the critical role of the interfragment bonds between waist-capping atoms in stabilizing the layer.

Journal Article↗