bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of molecular recognition: Steric electrostatic and hydrophobic complementarity
Authors: Náray‐Szabó Gábor 
Published: May 2005

AbstractWe discuss three important aspects of molecular recognition: steric, electrostatic and hydrophobic. Steric fit means that interacting atoms may not approach each other beyond their van der Waals radii and, simultaneously, crevices should be filled as densely as possible. Electrostatic fit requires the maximum ionic and polar (hydrogen bond or other) interaction between host and guest atoms while the hydrophobic fit corresponds to the association trend between apolar groups in an aqueous medium. Space‐filling models, obtained by molecular graphics, illustrate steric complementarity while we use molecular electrostatic potentials (MEPs) and fields (MEFs) to investigate electrostatic and hydrophobic matching. Molecular regions with negative and positive MEPs attract and repel a positive probe charge, respectively, so we consider them as attracting each other. Furthermore we postulate that regions with MEFs of similar magnitude tend to associate more strongly than those with very different fields (similis simili gaudet principle). We apply the above rules to the study of complementarity in the tryspin‐BPTI complex and in a crystalline association between styrene epoxide as guest and a comphor‐based anthracene derivative as host. We discuss molecular similarity on the same footing as complementarity and give some examples on the application of the concept of the rationalization of relative strengths of trypsin inhibitors.
Macromolecular crowding and molecular recognition
Authors: Minton Allen P. 
Published: May 2005

AbstractThe effects of macromolecular crowding upon macromolecular associations in solution, and upon binding of a macromolecular ligand to a surface site, ar ereviewed. It is demonstrated, by means of two examples, that crowding may lead to significant alterations of biochemical or biological recognition processes at the molecular level.
The making of the minibody: An engineered β‐protein for the display of conformationally constrained peptides
Authors: Tramontano Anna , Bianchi Elisabetta , Venturini Sara , Martin Franck , Pessi Antonelo , Sallozzo Maurizio 
Published: May 2005

AbstractConformationally constraining selectable peptides onto a suitable scaffold that enables their conformation to be predicted or readily determined by experimental techniques would considerably boost drug discovery process by reducing the gap between the discovery of a peptide lead and the design of a peptidomimetic with a more desirable pharmacological profile. With this in mind, we designed the minibody, a 61‐residue β‐protein aimed at retaining some desirable features of immunogloblin variable domains, such as tolerance to sequence variability in selected regions of the protein and predictability of main chain conformation of the same regions, based on the ‘canonical structures’ model. To test the ability of the minibody scaffold to support functional sites we also designed a metal binding version of the protein by suitably choosing the sequences of its loops. The minibody was produced both by chemical syntyhesis and expression in E. coli and charactgerized by size exclusion chromatography, UV CD (circular dichroism) spectroscopy and metal binding activity. All our data supported the model, but a more detailed structural characterization of the molecule was impaired by its low soubility. We were able to overcome this problem both by further; mutagenesis of the framework and by addition of a solublizing motif. The minibody is being used to select constrained human IL‐6 peptidic ligands from a library displayed on the surface of the f1 bacteriophage.
Analysis of the interaction between human interleukin‐5 and the soluble domain of its receptor using a surface plasmon resonance biosensor
Authors: Morton Thomas A. , Bennett Donald B. , Appelbaum Edward R. , Cusimano Donna M. , Johanson Kyung O. , Matico Rosalie E. , Young Peter R. , Doyle Michael , Chaiken Irwin M. 
Published: May 2005

AbstractA surface plasmon resonance (SPR) biosensor was used to study the interaction of human interleukin‐5 (hIL5) with its receptor. IL5 is a major growth factor in the production and activation of eosinophilis. The receptor for IL5 is composed of two subunits, α and β. The α subunit provides the specificity for IL5 and consist of an extracellular soluble domain, a single transmembrane region and a cytoplasmic tail. We expressed the soluble domain of the human IL5 receptor α subunit (shIL5Rα) and human IL5 (hIL5) in Drosophila. Both hIL5 and shIL5Rα were immobilized separately through amine groups onto the carboxylated dextran layer of sensor chips of the BIAcore™ (Pharmacia) SPR biosensor after N‐hydroxysuccinimide/carbodiimide activation of the chip surface. Interactions were measured for the complementary macromolecule, either shIL5Rα or hIL5, in solution. Kinetics of binding of soluble analyst to immobilized ligand were measured and from this the association rate constant, dissociation rate constant and equilibrium dissociation constant (Kd) were derived. With immobilized shIL5Rα and soluble hIL5, the measured Kd was 2 nM. A similar value was obtained by titration calorimetry. The Kd for Drosophila expressed receptor and IL5 is higher than the values reported for proteins expressed in different systems, likely due to differences in the methods of interaction analysis used for differences in protein glycosylation. Receptor‐IL5 binding was relatively pH independent between pH 6.5 and 9.5. Outside this range the dissociation rate increased with compressibility little increased in association rate. The values obtained for the interaction of hIL5 and shIL5Rα were found to depend on which component was immobilized; the Kd was 5.5 nM with immobilized hIL5 and soluble shIL5Rα. The SPR biosensor provides a unified methodology to measure the interaction properties of shIL5Rα and hIL5 derivatives, mutants and mimetic as well as to evaluate potential antagonists of the receptor‐cytokine interaction.
Structural and physicochemical analysis of the reaction between the anti‐lysozyme antibody D1.3 and the anti‐idiotopic antibodies E225 and E5.2
Authors: Tello Diana , Eisenstein Edward , Schwarz Frederick P. , Goldbaum Fernando A. , Fields Barry A. , Mariuzza Roy A. , Poljak Roberto J. 
Published: May 2005

AbstractThe reaction between the mouse (BALB/c) anti‐idiotiopic monoclonal antibodies E225 and E5.2 and idiotopes on the (BALB/c) anti‐lysozyme monoclonal antibody D1.3 has been characterized by titration calorimetry, by equilibrium sedimentation and by the determination of binding association and dissociation rates. The reaction between E5.2 and D1.3 is driven by a large negative enthalpy and its rate and equilibrium association constants are comparable to those observed in other antigen–antibody reactions. In contrast, the reaction between E225 and D1.3 is entropically driven and characterized by slow association kinetic (1 × 103 M−1 sec−1) and a resulting low equilibrium constant (Ka = 2 × 105M−1). A correlation of these properties with the three‐dimensional structure of the Fab225‐FabD1.3 complex, previously determined by X‐ray diffraction methods to 2.5 Å resolution, indicates that conformational changes of several D1.3 contacting residues, located in its complementarity determining regions, may explain these features of the reaction.
DNA recognition by DNase I
Authors: Suck Dietrich 
Published: May 2005

AbstractBovine pancreatic DNase I shows a strong preference for double‐stranded substrates and cleaves DNA with strongly varying cutting rates suggesting that the enzyme recognises sequence‐dependent structural variations of the DNA double helix. The complicated cleavage pattern indicates that several local as well as global helix parameters influences the cutting frequency of DNase I at a given bond. The high resolution crystal structures of two DNase I‐DNA complexes showed that the enzyme binds tightly in the minor groove, and to the sugar‐phosphate backbones of both strands, and thereby induces a widening of the minor groove and a bending towards the major grooves. In agreement with biochemical data this suggests that flexibility and minor groove geometry are major parameters determining the cutting rate of DNase I. Experimental observations showing that the sequence environmental of a dinucleotide step strongly affects its cleavage efficiency can be rationalized by that fact that six base pair are in contact with the enzyme. Mutational analysis based on the structural results has identified critical residues for DNA binding and cleavage and has lead to a proposal for the catalytic mechanism.
DNA recognition by intercalators and hybrid molecules
Authors: Waring Michael J. , Bailly Christian 
Published: May 2005

AbstractExperimental are described which probe the role of the 2‐amino group of guanine as a critical determinant of the recognition of nucleotide sequences in DNA by specific ligands. Homologous samples of tyrT DNA substituted with inosine or 26‐diaminopourine residues in place of guanosine or adenine respectively yield characteristically modified footprinting patterns when challenged with sequence‐selective antibiotics such as echinomycin, actinomycin or netrospin. The capacity of small molecules to recognise particular DNA sequences is exploited in the ‘combilexin’ strategy to target small molecules to defined sites in DNA. A composite molecule containing a distamycin moiety linked to an intercalating ellipticine derivative has been synthesised and shown to bind tightly to DNA but without much sequence‐selectivity. Refinement of this molecule based on predictions from molecular modelling has led to the synthesis of a second generation derivative bearing an additional positive charge: this new hybrid molecule is strongly selective for binding to AT‐rich tracts in DNA.
Analysing DNA complexes by circular and linear dichroism
Authors: Nordén Bengt , Kurucsev Tomas 
Published: May 2005

AbstractThe application of linear and circular dichroism (LD and CD) in nucleic acid research id illustrated by recent results aimed at answering specific structural problem in the interaction of DNA with molecules of biological importance. We first consider the circumstances under which ligands, such as DAPI (4′, 6‐diamidino‐2‐phenylindole), change their preferred binding mode in the minor groove to major groove binding or intercalation. As an extension of this problem we refer to the switch between groove binding and intercalation of structurally similar ligands such as ellipticines and trigonal ruthenium complexes. We also explore the use of LD and CD in the determination of the structure of the complex formed between the polynucleotide poly(dA) and the novel ‘peptide nucleic acid’, consisting of nucleic acid bases joined by a polyamide homomorphous with the deoxyribose‐phosphate backbone of DNA. Finally, the structure and interaction of the recombination enzyme RecA with DNA is discussed, in particular the influence of the presence of the intercalators, groove binders or covalent DNA adducts.
Buried surface analysis of HIV‐1 reverse transcriptase p66/p51 heterodimer and its interaction with dsDNA template/primer
Authors: Ding Jianping , Jacobo‐Molina Alfredo , Tantillo Chris , Lu Xiaode , Nanni Raymond G. , Arnold Edward 
Published: May 2005

AbstractThe p66/p51 human immunodeficiency virus type 1 reverse transcriptase is a heterodimer with identical N‐terminal amino acid sequences. The enzyme contains two polymerization domains and one RNase H domain, which is located at the C‐terminus of the p66 subunit. Both polymerization domains fold into four individual subdomains that are not arranged in a similar fashion, forming an unusually asymmetric dimer. The complexity of the RT p66/p51 heterodimer structure is simplified using solvent‐accessibility surface areas to describe the buried surface area of contact among the different subdomains. In addition, the RT/DNA contacts in the recently published RT/DNA/Fab structure. [Jacobo‐Molina et al., Proc. Natl Acad. Sci. USA 90, 6320–6324 (1993)] are described using the same approach. Finally, the RT/DNA complex is compared with other dimeric DNA‐binding proteins. It was found that the size of the protein and the extent of the dimer interface were not directly related to the extent of contact between the protein and the DNA. Furthermore, RT, the only protein that is not a sequence specific DNA binding protein in this analysis, had the largest surface of interaction with the nucleic acid.
Identification of a pharmacophore for nucleoside analog inhibitors directed at HIV‐1 reverse transcriptase
Authors: Fisher Mark A. , Yadav Prem N. S. , Yadav Janardan , Kristol David , Arnold Edward , Modak Mukund J. 
Published: May 2005

AbstractAn ‘active analog’ approach to receptor mapping was used to identify a pharmacophore for a set of thymidine nucleoside analog inhibitors of HIV‐1 reverse transcriptase. The preliminary results indicate that the O2, O4′, and O5′ atoms are capable of adopting a unique pharmacophoric pattern which may be the key to their recognition by reverse transcriptase.
Synthetic α‐helical peptides incorporating intercalators for DNA recognition
Authors: Brown Christopher L. , Harding Margaret M. 
Published: May 2005

AbstractThe design and synthesis of a water‐soluble 14‐residue peptide, in which a quinoline intercalator is attached to the peptide backbone via alkylation of a central cysteine residue, is reported. 600 MHz 1H NMR spectroscopy and circular dichroism indicate that the peptide forms a nascent helix in aqueous solution, ie. an ensemble of turn‐like structures over several adjacent residues in the peptide. A large number of sequential dNN(i, i+1) connectivities were observed in NOESY spectra, and titration of trifluoroethanol into a solution of the peptide resulted in the characteristic CD spectrum expected for an α‐helix. At low DNA concentrations, CD spectroscopy indicates that this helical conformation is stabilized, presumably due to folding of the peptide in the major groove of DNA.
The cofactor ATP in DNA‐RecA complexes is not intercalated between DNA bases
Authors: Takahashi Masayuki , Nordén Bengt 
Published: May 2005

AbstractIn an attempt to understand the role of ATP as a cofactor at the interaction of the RecA protein with DNA, we have studied the orientation geometries of the cofactor analogs adenosine 5′‐O‐(3‐thiotriphosphate) (ATPγS) and guanosine 5′‐O‐(3‐thiotriphosphate) (GTPγS) in RecA‐DNA complexes using flow linear dichroism spectroscopy. Both cofactors promote the formation of RecA‐DNA complexes of similar structure as judged from similar orientations of DNA bases. The DNA orientation was probed through the dichroism of the long‐wavelength absorption of a DNA analog, poly(dεA). In this way differences between the dichroic spectra of the ATPγS–RecA–DNA and GTPγS‐RecA‐DNA complexes, observed in the shorter‐wavelength region, are related to orientation at variations of the cofactor chromophores. The results show that the guanine plane of GTPγS is oriented parallel with the principal axis of the complex in contrast to the more perpendicular orientation of the DNA bases. This observation directly excludes the possibility that the cofactor could be intercalated between the DNA bases. This observation directly excludes the possibility that the cofactor could be intercalated between the DNA bases. The orientation of the adenine base of ATPγS, which may be similar to that of guanine of GTPγS albeit not exactly the same, is also inconsistent with intercalation. The possibility that the cofactor bound to the protein could be intercalated in DNA had been speculated from the observation that some DNA intercalators can induce RecA binding to DNA in the absence of cofator. There are probably no direct interactions between the cofator and the DNA bases and the role of the cofactor is probably related to interaction with RecA and a modification of protein conformation.
Conformational properties of topoisomerase II inhibitors and sequence specificity of DNA cleavage
Authors: Palumbo M. , Mabilia M. , Pozzan A. , Capranico G. , Tinelli S. , Zunino F. 
Published: May 2005

AbstractThe sequence specificity of topoisomerase‐II‐mediated DNA cleavage, stimulated by 2‐methyl‐9‐hydroxy ellipticinium and 4′, 5′,7‐trihydroyflavone (genistein) was investigated by sequencing analysis of DNA cleavage sites and molecular modeling techniques. The former drug exhibits a marked preference for a T base at the position immediately preceding the cleavage site (−1). The latter shares the preference for the same base, with an additional preference for a thymine at position +1. The cleavage intensity patterns for the two drugs differ considerably. From a conformational point of view, ellipticinium and genistein exhibit similar overall shape and dimensions. However, the fused ring system in the former generates a planar structure whereas the single bond, connecting the two aromatic portions in the latter, allows internal rotation. The most stable conformation of genistein corresponds to a deviation of about 40° from planarity. A computer‐assisted analysis was carried out to compare the steric and electrostatic properties of the two compounds. Two types of preferred (energetically almost degenerate) alignment for the two molecules were found. One corresponds to overlapping of the 9‐hydroxyl containing ring of ellipticinium with the 4′‐hydroxyphenyl moiety of genistein, the other envisages the same moiety of ellipticine superimposed to the hydroxyl‐benzopyrone portion of genistein. The structural similarities of the test drugs might account for the common preference for stimulation of DNA cleavage at position +1, whereas the different possible arrangements of genistein in the cleavable complex could explain both the additional +1 specificity exhibited by this compound and the differences in cleavage intensity patterns observed in comparison to ellipticinium.
Long‐range interactions between DNA‐bound ligands
Authors: Samuelson Per , Jensen Karl , Kubista Mikael 
Published: May 2005

AbstractWe have studied the interaction of the A:T specific minor‐groove binding ligand 4′, 6‐diamidino‐2‐phenylindole (DAPI) with synthetic DNA oligomers containing specific binding sites in order to investigate possible long‐range interactions between bound ligands. We find that DAPI binds cooperatively to the oligomers. The degree of cooperativity increases with increasing number of binding sites and decreases with the separation between them. This dependence is paralleled by changes in the induced circular dichroism spectrum of DAPI, which decreases in intensity at 335 nm and increases at 365 nm. These results are consistent with an allosteric interaction of DAPI with DNA, where bound ligands cooperatively alter the structure of the DNA molecule. This structural change seems possible to induce under various conditions, including physiological. One consequence of allosteric binding is that ligands bound at a distance from each other sense each other's presence and influence each other's properties. If some regulatory proteins the same conformational change as DAPI, novel mechanisms for controlling gene expression can be anticipated.
Computer modelling of kappa carrageenam‐mannan interactions
Authors: Turquois Tristan , Rochas Cyrille , Taravel François‐R. , Tvaroska Igor 
Published: May 2005

AbstractMolecular modelling has been used as a theoretical approach to investigate the kappa carrageenan structure and its interaction with mannan chains. Calculations revealed the existence of six minima for the kappa carrageenan structure in solution. Two of them were very close to the structure found in the solid state. The methodology allowed the calculation of the theoretical counterpart of the structures based on x‐ray fibre diffractions studies. In the second step of this study, we have shown that there is the possibility of interactions between kappa carrageenan double helices and mannan chains. This interacting process is allowed by the flexibility of the mannan chains and structural changes of the kappa carrageenan double helices. The calculations suggest that the disaccaride mannan fragment might be required for recognition. The result of our investigation are in good agreement with a model of gel structure based on experimental data. This approach could be applied to simulate and predict other associations in molecular assemblies.
Specificity in the recognition of crystals by antibodies
Authors: Kam Michal , Perl‐Treves Daniele , Sfez Ruth , Addadi Lia 
Published: May 2005

AbstractWe show that IgG molecules isolated from the serum of rabbits injected with crystals of monosodium urate monohydrate, magnesium urate octahydrate and allopurinol, can each catalyze the nucleation of the same type of crystal to which they were exposed. These results generalize previous findings related to monosodium urate monohydrate and assess the idea that the invasion of a foreign crystal into an organism may amplify a population of antibodies which bear in their binding sites an imprint of the crystal surface structure. Such antibodies further act as nucleating templates which accelerate crystal formation in vitro. Antibodies from rabbitscan injected with sodium urate crystals do not cross‐react or cross‐react only to a low extent with antibodies isolated from rabbits injected with crystals of either magnesium urate or allopurinol. These results indicate a high specificity of the elicited antibodies, as these can distinguish between nuclei of crystals having similar molecular and structural characteristics.
Binding of malate dehydrogenase and NADH channelling to complex I
Authors: Ovádi Judit , Huang Yongwei , Spivey H. Olin 
Published: May 2005

AbstractAs previously reported, mitochondrial malate dehydrogenase (MDH) binds to purified complex I of the electron transport system. With conditions used in previous reports, MDH binds even more extensively, but probably predominantly non‐specifically, to the matrix side of the inner mitochondrial membrane of submitochodrial particles (SMP). Herein we report experimental conditions for highly specific binding of malate dehydrogenase to complex I within SMP. These conditions permit us to demonstrate NADH channelling from malate dehydrogenase to complex I using the completing reaction test. This test, though not ideal for all situations, has several advantages over the enzyme buffering test previously used. These advantages should facilitate further studies elucidating NADH channeling to complex I from MDH and other dehydrogenases. Independent evidence of NADH channelling to the electron transport chain and the potential advantages of substrate channelling in general are also discussed. Substrate channelling from MDH in particular may be especially beneficial because of the unfavourable equilibrium and kinetics of this enzyme reaction.
Immunoglobulin‐like domain is present in the extracellular part of the receptor tyrosine kinase from the marine sponge geodia cydonium
Authors: Schäcke Heike , Rinkevich Baruch , Gamulin Vera , Müller Isabel M. , Müller Werner E. G. 
Published: May 2005

AbstractWe have isolated and characterized two cDNAs from the marine sponge Geodia cydonium coding for a new member of a receptor tyrosine kinase of class II. The deduced amino acid sequence shows two characteristic domains: (i) the tyrosine kinase domain; and (ii) and immunoglobulin‐like domain. The latter part shows high homology to the vertebrate C2 type immunoglobulin domain. This result demonstrates that immunoglobulin domains are not recent achievements of higher animals but exist also in those animals which have diverged from other organisms about 800 million years ago.