Positron-molecule bound states and positive ion production

The interaction was studied of low energy positrons with large molecules such as alkanes. These data provide evidencce for the existence of long lived resonances and bound states of positrons with neutral molecules. The formation process and the nature of these resonances are discussed. The positive ions produced when a positron annihilates with an electron in one of these resonances were observed and this positive ion formation process is discussed. A review is presented of the current state of the understanding of these positron-molecule resonances and the resulting positive ion formation. A number of outstanding issues in this area is also discussed

Two distinct DNA sequences recognized by transcription factors represent enthalpy and entropy optima

Most transcription factors (TFs) can bind to a population of sequences closely related to a single optimal site. However, some TFs can bind to two distinct sequences that represent two local optima in the Gibbs free energy of binding (Delta G). To determine the molecular mechanism behind this effect, we solved the structures of human HOXB13 and CDX2 bound to their two optimal DNA sequences, CAATAAA and TCGTAAA. Thermodynamic analyses by isothermal titration calorimetry revealed that both sites were bound with similar Delta G. However, the interaction with the CAA sequence was driven by change in enthalpy (Delta H), whereas the TCG site was bound with similar affinity due to smaller loss of entropy (Delta S). This thermodynamic mechanism that leads to at least two local optima likely affects many macromolecular interactions, as Delta G depends on two partially independent variables Delta H and Delta S according to the central equation of thermodynamics, Delta G = Delta H - T Delta S.Peer reviewe

Effect of the Dielectric-Constant Mismatch and Magnetic Field on the Binding Energy of Hydrogenic Impurities in a Spherical Quantum Dot

Within the effective mass approximation and variational method the effect of dielectric constant mismatch between the size-quantized semiconductor sphere, coating and surrounding environment on impurity binding energy in both the absence and presence of a magnetic field is considered. The dependences of the binding energy of a hydrogenic on-center impurity on the sphere and coating radii, alloy concentration, dielectric-constant mismatch, and magnetic field intensity are found for the GaAs-Ga_(1-x)Al_(x)As-AlAs (or vacuum) system

DNABINDPROT: fluctuation-based predictor of DNA-binding residues within a network of interacting residues

DNABINDPROT is designed to predict DNA-binding residues, based on the fluctuations of residues in high-frequency modes by the Gaussian network model. The residue pairs that display high mean-square distance fluctuations are analyzed with respect to DNA binding, which are then filtered with their evolutionary conservation profiles and ranked according to their DNA-binding propensities. If the analyses are based on the exact outcome of fluctuations in the highest mode, using a conservation threshold of 5, the results have a sensitivity, specificity, precision and accuracy of 9.3%, 90.5%, 18.1% and 78.6%, respectively, on a dataset of 36 unbound–bound protein structure pairs. These values increase up to 24.3%, 93.4%, 45.3% and 83.3% for the respective cases, when the neighboring two residues are considered. The relatively low sensitivity appears with the identified residues being selective and susceptible more for the binding core residues rather than all DNA-binding residues. The predicted residues that are not tagged as DNA-binding residues are those whose fluctuations are coupled with DNA-binding sites. They are in close proximity as well as plausible for other functional residues, such as ligand and protein–protein interaction sites. DNABINDPROT is free and open to all users without login requirement available at: http://www.prc.boun.edu.tr/appserv/prc/dnabindprot/

Molecular basis of halorespiration control by CprK, a CRP-FNR type transcriptional regulator

Certain bacteria are able to conserve energy via the reductive dehalogenation of halo-organic compounds in a respiration-type metabolism. The transcriptional regulator CprK from Desulfitobacterium spp. induces expression of halorespiratory genes upon binding of o-chlorophenol ligands and is reversibly inactivated by oxygen through disulphide bond formation. We report crystal structures of D. hafniense CprK in the ligand-free (both oxidation states), ligand-bound (reduced) and DNA-bound states, making it the first member of the widespread CRP-FNR superfamily for which a complete structural description of both redox-dependent and allosteric molecular rearrangements is available. In conjunction with kinetic and thermodynamic ligand binding studies, we provide a model for the allosteric mechanisms underpinning transcriptional control. Amino acids that play a key role in this mechanism are not conserved in functionally distinct CRP-FNR members. This suggests that, despite significant structural homology, distinct allosteric mechanisms are used, enabling this protein family to control a very wide range of processes

Molecular basis of halorespiration control by CprK, a CRP-FNR type transcriptional regulator

Certain bacteria are able to conserve energy via the reductive dehalogenation of halo-organic compounds in a respiration-type metabolism. The transcriptional regulator CprK from Desulfitobacterium spp. induces expression of halorespiratory genes upon binding of o-chlorophenol ligands and is reversibly inactivated by oxygen through disulphide bond formation. We report crystal structures of D. hafniense CprK in the ligand-free (both oxidation states), ligand-bound (reduced) and DNA-bound states, making it the first member of the widespread CRP-FNR superfamily for which a complete structural description of both redox-dependent and allosteric molecular rearrangements is available. In conjunction with kinetic and thermodynamic ligand binding studies, we provide a model for the allosteric mechanisms underpinning transcriptional control. Amino acids that play a key role in this mechanism are not conserved in functionally distinct CRP-FNR members. This suggests that, despite significant structural homology, distinct allosteric mechanisms are used, enabling this protein family to control a very wide range of processes

A DNA minor groove electronegative potential genome map based on photo-chemical probing

The double-stranded DNA of the genome contains both sequence information directly relating to the protein and RNA coding as well as functional and structural information relating to protein recognition. Only recently is the importance of DNA shape in this recognition process being fully appreciated, and it also appears that minor groove electronegative potential may contribute significantly in guiding proteins to their cognate binding sites in the genome. Based on the photo-chemical probing results, we have derived an algorithm that predicts the minor groove electronegative potential in a DNA helix of any given sequence. We have validated this model on a series of protein–DNA binding sites known to involve minor groove electrostatic recognition as well as on stable nucleosome core complexes. The algorithm allows for the first time a full minor groove electrostatic description at the nucleotide resolution of any genome, and it is illustrated how such detailed studies of this sequence dependent, inherent property of the DNA may reflect on genome organization, gene expression and chromosomal condensation

Recognition models to predict DNA-binding specificities of homeodomain proteins

Motivation: Recognition models for protein-DNA interactions, which allow the prediction of specificity for a DNA-binding domain based only on its sequence or the alteration of specificity through rational design, have long been a goal of computational biology. There has been some progress in constructing useful models, especially for C2H2 zinc finger proteins, but it remains a challenging problem with ample room for improvement. For most families of transcription factors the best available methods utilize k-nearest neighbor (KNN) algorithms to make specificity predictions based on the average of the specificities of the k most similar proteins with defined specificities. Homeodomain (HD) proteins are the second most abundant family of transcription factors, after zinc fingers, in most metazoan genomes, and as a consequence an effective recognition model for this family would facilitate predictive models of many transcriptional regulatory networks within these genomes

Evolution of a Novel Appendage Ground Plan in Water Striders Is Driven by Changes in the Hox Gene Ultrabithorax

Water striders, a group of semi-aquatic bugs adapted to life on the water surface, have evolved mid-legs (L2) that are long relative to their hind-legs (L3). This novel appendage ground plan is a derived feature among insects, where L2 function as oars and L3 as rudders. The Hox gene Ultrabithorax (Ubx) is known to increase appendage size in a variety of insects. Using gene expression and RNAi analysis, we discovered that Ubx is expressed in both L2 and L3, but Ubx functions to elongate L2 and to shorten L3 in the water strider Gerris buenoi. Therefore, within hemimetabolous insects, Ubx has evolved a new expression domain but maintained its ancestral elongating function in L2, whereas Ubx has maintained its ancestral expression domain but evolved a new shortening function in L3. These changes in Ubx expression and function may have been a key event in the evolution of the distinct appendage ground plan in water striders

Ligand-binding domain subregions contributing to bimodal agonism in cyclic nucleotide–gated channels

Cyclic nucleotide–gated (CNG) channels bind cGMP or cAMP in a cytoplasmic ligand–binding domain (BD), and this binding typically increases channel open probability (Po) without inducing desensitization. However, the catfish CNGA2 (fCNGA2) subtype exhibits bimodal agonism, whereby steady-state Po increases with initial cGMP-binding events (“pro” action) up to a maximum of 0.4, but decreases with subsequent cGMP-binding events (“con” action) occurring at concentrations >3 mM. We sought to clarify if low pro-action efficacy was either necessary or sufficient for con action to operate. To find BD residues responsible for con action or low pro-action efficacy or both, we constructed chimeric CNG channels: subregions of the fCNGA2 BD were substituted with corresponding sequence from the rat CNGA4 BD, which does not support con action. Constructs were expressed in frog oocytes and tested by patch clamp of cell-free membranes. For nearly all BD elements, we found at least one construct where replacing that element preserved robust con action, with a ratio of steady-state conductances, g(10 mM cGMP)/g(3 mM cGMP) < 0.75. When all of the BD sequence C terminal of strand β6 was replaced, g(10 mM cGMP)/g(3 mM cGMP) was increased to 0.95 ± 0.05 (n = 7). However, this apparent attenuation of con action could be explained by an increase in the efficacy of pro action for all agonists, controlled by a conserved “phosphate-binding cassette” motif that contacts ligand; this produces high Po values that are less sensitive to shifts in gating equilibrium. In contrast, substituting a single valine in the N-terminal helix αA abolished con action (g(30 mM cGMP)/g(3 mM cGMP) increased to 1.26 ± 0.24; n = 7) without large increases in pro-action efficacy. Our work dissociates the two functional features of low pro-action efficacy and con action, and moreover identifies a separate structural determinant for each