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At least 253 records · Page 14Linked to original sources
PubMed1987

Drosophila mitochondrial DNA: conserved sequences in the A + T-rich region and supporting evidence for a secondary structure model of the small ribosomal RNA.

The sequence of a segment of the Drosophila virilis mitochondrial DNA (mtDNA) molecule that contains the A + T-rich region, the small rRNA gene, the tRNA(f-met), tRNA(gln), and tRNA(ile) genes, and portions of the ND2 and tRNA(val) genes is presented and compared with the corresponding segment of the D. yakuba mtDNA molecule. The A + T-rich regions of D. virilis and D. yakuba contain two correspondingly located sequences of 49 and 276/274 nucleotides that appear to have been conserved during evolution. In each species the replication origin of the mtDNA molecule is calculated to lie within a region that overlaps the larger conserved sequence, and within this overlap is found a potential hairpin structure. Substitutions between the larger conserved sequences of the A + T-rich regions, the small mt-rRNA genes, and the ND2 genes are biased in favor of transversions, 71-97% of which are A----T changes. There is a 13.8 times higher frequency of nucleotide differences between the 5' halves than between the 3' halves of the D. virilis and D. yakuba small mt-rRNA genes. Considerations of the effects of observed substitutions and deletion/insertions on possible nucleotide pairing within the small mt-rRNA genes of D. virilis and D. yakuba strongly support the secondary structure model for the Drosophila small mt-rRNA that we previously proposed.

Adenine↗
PubMed1982

A structural model of 5S RNA from E. coli based on intramolecular crosslinking evidence.

We describe new results obtained using the bifunctional chemical reagent phenyldiglyoxal (PDG) to study the intramolecular crosslinking of ribosomal 5S RNA from E. coli. In a previous publication (Wagner & Garrett [1]) we reported the identification of a crosslink in the stem region of 5S RNA (G2-G112) using the same reagent but were unable to obtain further information because of the presence of monofunctional adducts which confused the analyses. To overcome this problem, we have removed the monoaddition products by coupling them via their free reagent ends to a solid support bearing reactive groups. Using this system we have been able to identify a new crosslink G41-G72 in native 5S RNA which has considerable structural implications. We propose a structural model in which the proximity of both nucleotides is maintained by secondary interactions.

Base Sequence↗
PubMed1996

Structure model of a complex between the factor for inversion stimulation (FIS) and DNA: modeling protein-DNA complexes with dyad symmetry and known protein structures.

A method is presented to predict overall conformations of protein-DNA complexes on the basis of the known three-dimensional structures of the proteins. The method is restricted to proteins with a common twofold symmetry axis, which show only minor conformational changes upon binding to DNA. The method uses a numerical finite difference solution of the linearized Poisson-Boltzmann equation and subsequent energy minimization cycles. Structural parameters-the rotation angle of the DNA relative to the protein around the common symmetry axis, the protein-DNA distance, and intermolecular hydrogen-bonding contacts-are presented for two test cases, DNA bound to CAP (catabolite gene activator protein) and to the Cro-repressor of bacteriophage 434. The DNA curvature in the starting model of the docking procedure was chosen as a smoothed approximation of the conformation found in the X-ray structures of these complexes. The method is further used to predict the unknown structure of the complex between the factor for inversion stimulation (FIS) and DNA, which is bent upon binding to FIS. In contrast to the test cases, the unknown curvature of the starting model is derived from a calibration of electrostatic precalculations for different proteins according to crystallographically observed DNA bending. The results of the modeling are in good accordance with the experimentally observed overall structure of protein-DNA complexes for the two test cases; for FIS, they correspond to several of the experimentally proposed protein-DNA contacts.

DNA↗
PubMed1999

Selectivity of von Willebrand factor triplet bands towards heparin binding supports structural model.

Human plasma-derived von Willebrand factor (hp-vWF) and recombinant von Willebrand factor (r-vWF) have been fractionated by heparin affinity chromatography followed by multimer analysis using SDS-agarose gel electrophoresis. Because heparin binding sites are contained in each vWF subunit, high molecular weight multimers of r-vWF and hp-vWF, respectively, were eluted with higher salt concentration, in comparison to r-vWF and hp-vWF molecules with a low degree of multimerization. Heparin affinity chromatography did not affect the multimer composition of r-vWF. By contrast, faster migrating satellite bands and slower migrating satellite bands of hp-vWF exhibited reduced and increased heparin affinity, respectively, compared to the intermediate band of the same triplet. Because heparin binding sites are localised in the N-terminal domain of the hp-vWF subunit, this result confirms a structural model of hp-vWF (Fischer et al., Biochem. J. 1998;331:483-488) suggested recently, in which the slower migrating satellite bands have excess of one N-terminal fragment and the faster migrating satellite bands lack one N-terminal fragment, respectively, in comparison with the corresponding intermediate triplet band.

Binding Sites↗
PubMed1997

Secondary structure and shape of plasma sex steroid-binding protein--comparison with domain G of laminin results in a structural model of plasma sex steroid-binding protein.

We have analyzed the secondary structure, shape and dimensions of plasma sex steroid-binding protein (SBP) by CD, size-exclusion chromatography and electron microscopy. CD spectra show extrema at 186 nm and 216 nm characteristic for beta-sheet structures. Analysis with different algorithms indicates 15% alpha-helix, 43% beta-sheet and 10-16% beta-turn structures. An irreversible structural change is observed upon heating above 60 degrees C, which correlates with the loss of steroid-binding activity. As the SBP sequence shows similarity with domains of several multidomain proteins, including laminins, we evaluated the structure of domain G of laminin-1. The CD spectrum shows extrema at 200 nm and 216 nm. Deconvolution results in 13% alpha-helix, 32% beta-sheet and 15% beta-turn structures. Steroid-binding assays indicate that laminin and fragments thereof have no activity. Size-exclusion chromatography reveals that SBP has an extended shape and can be modeled as a cylinder with a length and diameter of 23 nm and 3 nm, respectively. This shape and the dimensions are in agreement with the appearance on electron micrographs. We propose a model for the structure of SBP in which two monomers assemble head to head with the steroid-binding site located in the center of the rod-like particle.

Amino Acid Sequence↗
PubMed1985

Model structure for the inflammatory protein C5a.

The complement cleavage product C5a is a potent stimulant of inflammatory processes; thus, inhibition of C5a activity is of therapeutic interest. The three-dimensional structure of the major portion of C5a was modeled from the homologous C3a crystal structure by comparative modeling techniques. The model shows that core residues of C5a are completely conserved, while external residues differ from C3a. Even though the amino-terminal 12 residues of C3a are disordered in the crystal, this sequence in C5a may form an amphipathic helix. The distribution of species sequence differences in the complete C5a structure suggests a possible receptor binding site.

Amino Acid Sequence↗
PubMed1988

Purification, sequence, and model structure of charybdotoxin, a potent selective inhibitor of calcium-activated potassium channels.

Charybdotoxin (ChTX), a protein present in the venom of the scorpion Leiurus quinquestriatus var. hebraeus, has been purified to homogeneity by a combination of ion-exchange and reversed-phase chromatography. Polyacrylamide gel electrophoresis, amino acid analysis, and complete amino acid sequence determination of the pure protein reveal that it consists of a single polypeptide chain of 4.3 kDa. Purified ChTX is a potent and selective inhibitor of the approximately 220-pS Ca2+-activated K+ channel present in GH3 anterior pituitary cells and primary bovine aortic smooth muscle cells. The toxin reversibly blocks channel activity by interacting at the external pore of the channel protein with an apparent Kd of 2.1 nM. The primary structure of ChTX is similar to a number of neurotoxins of diverse origin, which suggests that ChTX is a member of a superfamily of proteins that modify ion-channel activities. On the basis of this similarity, the three-dimensional structure of ChTX has been modeled from the known crystal structure of alpha-bungarotoxin. These studies indicate that ChTX is useful as a probe of Ca2+-activated K+-channel function and suggest that the proposed tertiary structure of ChTX may provide insight into the mechanism of channel block.

Amino Acid Sequence↗
PubMed1995

Incorporation of diacids into the polyglycine II structure: model studies.

Aliphatic diacids are often incorporated into polypeptide structures in order to obtain model compounds for hormones, protein turns, etc. They are also fundamental components of many commercial polyamides. On the other hand glycine, the simplest amino acid, shows unique conformational features. In order to better understand the structure of such compounds, we have synthetized and determined the molecular structure of three models represented by the general formula CH3-CH2-CH2-NH-CO-CH2-NH-CO-(CH2)n-2-CO-NH-CH2-CO-NH-CH2-CH2-CH3, with n = 3, 4, or 6. Conformational differences have been found in the dicarboxylic moiety, whereas glycine always has the polyglycine II conformation. The -CO-(CH2)n-2-CO-segment adopts a folded conformation: SS, TGT, and SGTGS for n = 3, 4, and 6, respectively. Molecular packing is always pseudohexagonal and a network of hydrogen bonds oriented in three directions at 120 degrees is formed. The results are of interest in order to provide information about polyamides in which glycine residues are incorporated. Our results confirm the tendency of glycine residues to adopt the polyglycine II conformation in its copolymers with aliphatic compounds.

Amino Acid Sequence↗
PubMed1983

Refined secondary structure models for the 16S and 23S ribosomal RNA of Escherichia coli.

The complete range of published sequences for ribosomal RNA (or rDNA), totalling well over 50,000 bases, has been used to derive refined models for the secondary structures of both 16S and 23S RNA from E. coli. Particular attention has been paid to resolving the differences between the various published secondary structures for these molecules. The structures are described in terms of 133 helical regions (45 for 16S RNA and 88 for 23S RNA). Of these, approximately 20 are still tentative or unconfirmed. A further 20 represent helical regions which definitely exist, but where the detailed base-pairing is still open to discussion. Over 90 of the helical regions are however now precisely established, at least to within one or two base pairs.

Animals↗
PubMed1995

Structural models of Na+, Ca2+, and K+ channels.

The structure determination of voltage-gated channels by the combination of molecular modeling and mutagenesis experiments is a long term, iterative process. As such, the models should be considered as a work in progress, with changes expected as more data becomes available. The primary role of the models is that they assimilate the known data and provide ideas for further experiments to elucidate the real structures. Although the models presented here have already gone through two or three cycles of development and testing, many aspects remain tentative. Perhaps the most significant result so far is that the P segment was experimentally confirmed to form the ion-selective part of the channel. In a subsequent cycle of testing and modeling, the specific residues responsibility for Na+ and Ca2+ selectivity have been identified and the selectivity filter of K+ channels is now predicted to be formed by the side chains, but rather by the carbonyl oxygens of the conserved Gly-Tyr-Gly sequence backbone. As another example, the 9p residue of the P segment of K+ channels was originally modeled as either being buried in the protein or accessible channels was originally modeled as either being buried in the protein or accessible from inside the cell only. However, once mutation of this residue to histidine was found to affect blockade by extracellular TEA, protons, Zn2+ and histidine reagents (DeBiasi et al., 1993), the models were updated to have this and the hydrophilic residues in the first part of P form a helix that comprises part of the extracellular, outer vestibular of the pore. While this motif was used also for Na+ and Ca2+ pore models (see Fig. 2) where the putative helices are amphipathic, it remains to be verified. Modeling of the size and shape of the outer vestibule of K+ channels was also aided by the data for the binding of CTX in the extracellular entrance to the pore. Similarly, experiments with peptide toxins such as mu and omega conotoxins may prove useful in modeling the outer vestibules of the Na+ and/or Ca2+ channels. While important advances have been made, it is important to realize that these approaches are still very new. In the future we are likely to see improvements on both the theoretical and experimental sides which will greatly advance the process.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1987

Molecular genetics of the VDAC ion channel: structural model and sequence analysis.

The voltage-dependent anion-selective channel of the outer mitochondrial membrane provides a unique system in which to study the molecular basis of voltage gating of ion flow. We have cloned and sequenced a cDNA coding for this protein in yeast. From the derived amino acid sequence, we have generated a preliminary model for the secondary structure of the protein which suggests that the protein forms a "beta-barrel" type structure. Comparison of the VDAC amino acid sequence with that of the bacterial porins has indicated that the two classes of molecules appear to be unrelated.

Amino Acid Sequence↗
PubMed1991

An initial slope method for model structure: independent estimation of the elimination rate constant of a metabolite.

A model structure-independent method for calculating the true elimination rate constant of a primary metabolite is presented. It does not require direct metabolite administration and uses data on drug and metabolite blood (plasma) concentrations after a bolus drug input. The method has been tested and compared with the moment method and the area function method using errorless and errant data simulated on the basis of one- and two-compartment models of the metabolite kinetics. In contrast to known methods the proposed method provided exact estimates of the elimination rate constant in the case of errorless data of both one- and two-compartment models. However the estimates are sensitive to random errors in the concentration data.

Mathematical Computing↗
PubMed1991

Structured model for cell growth and enzyme production by recombinant Escherichia coli.

A structured cell model has been developed to describe the cultivation of recombinant Escherichia coli K12 with multicopy plasmid under the control of a lambda PR-promoter and a temperature-sensitive lambda cI 857 repressor. The model, based on measurements of a batch culture in a stirred tank reactor, allows statements to be made on the time variation of intracellular processes. Based on cell regulation, the substrate transfer into the cell was considered to be the rate-limiting step for substrate utilization. The model describes substrate utilization, cell growth, and product formation by means of a system of time-dependent, coupled, and partly non-linear differential equations. The solution of these equations allows calculation of the time variation of the concentrations of substrates (glucose and amino acids), dissolved oxygen and cells in the broth as a function of time and the process parameters.

Cell Division↗
PubMed1976

Structural model of vestibular effects on the blood pressure.

The model described in the present work is a structural presentation of certain aspcets of the vesibular effects on the blood pressure. The model comprises the joint action of the otolith system and the semicircular canals, gangl. Scarpe, the vestibular nuclei, the vasomotor centre and the nuclei of n. vagus. The direct transfer of information both from gangl. Scarpe to the vasoregulating centre and from nucl. Schwalbe to the vagal nuclei, as well as its polysynaptic transmission, are considered. The model examines a case when only two factors, namely decrease in the heart rate controlled by n. vagus and decrease in the heart tone controlled by the vasoregulating centre, determine the effect of blood pressure drop after vestibular stimulation. The structure of the model is flexible and permits its elaboration by including additional factors for the blood pressure drop.

Blood Pressure↗
PubMed1996

A quantitative model of the "effective" signal processing in the auditory system. I. Model structure.

This paper describes a quantitative model for signal processing in the auditory system. The model combines a series of preprocessing stages with an optimal detector as the decision device. The present paper gives a description of the various preprocessing stages and of the implementation of the optimal detector. The output of the preprocessing stages is a time-varying activity pattern to which "internal noise" is added. In the decision process, a stored temporal representation of the signal to be detected (template) is compared with the actual activity pattern. The comparison amounts to calculating the correlation between the two temporal patterns and is comparable to a "matched filtering" process. The detector itself derives the template at the beginning of each simulated threshold measurement from a suprathreshold value of the stimulus. The model allows one to estimate thresholds with the same signals and psychophysical procedures as those used in actual experiments. In the accompanying paper [Dau et al., J. Acoust. Soc. Am. 99, 3623-3631 (1996)] data obtained for human observers are compared with the optimal-detector model for various masking conditions.

Auditory Perception↗
PubMed1986

Polydepsipeptides. 13. Synthesis and 1H-n.m.r. analysis of collagen model structures.

The synthesis of three collagen model analogs is described: Ac-Ala-Gly-Pro-Ala-Gly-Pro-NHMe, Ac-Ala-Gly-Pro-Ala-Glc-Pro-NHMe, and Ac-Ala-Glc-Pro-Ala-Gly-Pro-NHMe, where Glc stands for glycolic acid. The 1H-n.m.r. properties of these compounds in dimethylsulfoxide-d6 and trifluoroethanol are described. While in DMSO-d6 the compounds are random, in TFE the glycine amide protons seem to be less solvent exposed than the other amide protons. Little difference was found in the behavior of the three compounds.

Amino Acid Sequence↗
PubMed1996

Model structure of decorin and implications for collagen fibrillogenesis.

The three-dimensional structure of human decorin, a secreted proteoglycan involved in the regulation of collagen fibrillogenesis and cellular growth, has been modeled based on the crystal structure of the porcine ribonuclease inhibitor. Both proteins contain leucine-rich repeats and share 18% identical residues. This model structure of decorin has an arch shape with the single glycosaminoglycan chain and the three N-linked oligosaccharides located on the same side of the molecule. Decorin was modeled as binding to a polar sequence of collagen type I found in the d band. The inner concave surface is the appropriate size and shape to accommodate only one collagen triple helix of approximately 3 nm in length. The binding of one collagen triple helix to decorin is proposed to play a major role in the formation of the staggered arrangement of collagen molecules within the microfibrils by preventing lateral fusion of collagen molecules.

Amino Acid Sequence↗
PubMed1994

Molecular dynamics studies on peroxidases: a structural model for horseradish peroxidase and a substrate adduct.

Molecular dynamics (MD) calculations are performed on cytochrome c peroxidase (CcP) and on horseradish peroxidase, isoenzyme C (HRP), and its substrate adduct with p-cresol. For CcP, a refinement in solution of the X-ray structure is obtained which indicates that in solution the protein structure is very similar to that in the crystal. For HRP, the X-ray structure is not available. We have generated a model of this protein based on the recently reported structure of the similar lignin peroxidase (LiP) protein. This model involves the entire system as all the amino acid residues match the sequence. This HRP model was refined through energy minimization and MD calculations. A refined structural model for HRP, for the first time involving the entire protein, is therefore now available. The tertiary structure of HRP is close to that of LiP, and also the active site in the two proteins has significantly similar structures. The well-ordered water molecules and the extensive H-bond network present in the X-ray structure of CcP is maintained in the dynamics without any constraints, indicating that the active site residues produce a field strong enough to make all these interactions quite stable. Interestingly, also in HRP a network of ordered water molecules and H-bonds is present, again without constraints. This is consistent with the similarities of the active sites in the two proteins. Finally, we have calculated the MD structure of the adduct of HRP and a substrate molecule, p-cresol. This structural model is compared with the NMR data, which are in fairly good agreement. The binding site and the protein-substrate interactions are discussed.

Binding Sites↗