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C Blomberg

Publications and source records attributed to C Blomberg.

36 records · Page 2Linked to original sources
PubMed1980

Thermodynamic constraints on kinetic proofreading in biosynthetic pathways.

We develop a quantitative theory of kinetic proofreading with an arbitrary number of checking steps after the hydrolysis of a nucleoside triphosphate. In particular, we investigate the relationship between the minimum dissipation of free energy required for a given error frequency in such systems. Several conclusions can be drawn from the present treatment: first, the ultimate accuracy of error correcting selective pathways is set by the displacement from equilibrium of the nucleoside triphosphates. Second, it is advantageous to achieve a desired accuracy at a small energy dissipation with several checking steps rather than a single one. This could explain antinomies in the amino acylation reaction as well as in mRNA translation, where small structural differences lead to large differences in flow rates between right and wrong substrates. Third, all checking steps should contribute equally to the accuracy, which implies a specific and symmetrical set of rate constants for the checking events on the enzyme.

Acylation↗
PubMed1979

Trans-membrane translocation of proteins. The direct transfer model.

As a start towards a deeper understanding of the transmembrane transport of proteins, the transfer of a nascent chain through the lipophilic core of a membrane is discussed from a physico-chemical point of view. Some simple considerations of the energetics of protein structure, together with experimental data on the transfer process, form the basis for a detailed and quantifiable model, accounting for the extrusion of secreted proteins as well as for the insertion of trans-membrane proteins.

Amino Acid Sequence↗
PubMed1978

Association kinetics with coupled diffusion III. Ionic-strength dependence of the lac repressor-operator association.

The repressor-operator association is treated in a model where the repressor molecule can find its specific binding site, the operator, on a large DNA chain by performing a one-dimensional diffusion along the chain. The ionic-strength dependence is calculated by introducing a screened electrostatic potential around the DNA chain and coupling the free diffusion of the repressor in this potential to the proposed one-dimensional diffusion along the chain. The main influence on the association rate comes from the competitive binding of ions to the unspecific DNA sites. It is also demonstrated that during the time that the repressor is bound in a global sense, the diffusion along the chain will be made up of a strictly one-dimensional motion over fairly short distances, interspersed with many local dissociations during which the repressor in essence is free in solution.

Binding Sites↗
PubMed1978

Models for mRNA translation: theory versus experiment.

Three models for mRNA translation are discussed in the light of available experimental data. It is concluded that the elongation rates vary along a messenger, possibly as a result of a coupling between ribosome movement and mRNA secondary structure. Some promising areas of further experimentation are indicated.

Alpha-Globulins↗
PubMed1977

Association kinetics with coupled diffusion. An extension to coiled-chain macromolecules applied to the lac repressor-operator system.

The association of a molecule onto a specified binding site on a large chain-like macromolecule is described in the "sliding" model, where the molecule is allowed to move along the chain in a one-dimensional diffusion which is coupled to the three-dimensional diffusion in solution. The present work extends a previous one by treating the chains more generally as coiled instead of straight. The model is applied to the lac repressor-operator association. A general expression for the rate of unspecific attachment to a chain-like macromolecule is also derived.

DNA, Bacterial↗
PubMed1976

Association kinetics with coupled diffusional flows. Special application to the lac repressor--operator system.

The time development of the association of the lac repressor to the operator is considered in a model where the repressor is allowed to bind unspecifically to DNA and move along the DNA chain in a one-dimensional diffusion. The coupling to the three-dimensional diffusion outside the chain is introduced by letting the repressor associate and dissociate from the chain until it is finally bound to the operator. All distance correlations along the chain are included. The mean time of association is calculated and through a comparison with experimental data the molecular parameters are determined. The one-dimensional diffusion constant is found to be of the order of 10(-9) cm(2)s(-1). The model is sufficiently general to be applicable to other similar systems.

Diffusion↗
PubMed1975

Allosteric mechanism for codon-dependent tRNA selection on ribosomes.

We suggest that the interaction between a codon and its cognate tRNA induces conformational changes in the tRNA. We further suggest that sites on the ribosome preferentially bind tRNA in those conformations which require proper matching of codon and anticodon. According to this model, the codon functions as an allosteric effector which influences the conformation at various sites in the tRNA. This is made possible by the ribosome, which we suggest traps tRNA molecules in those conformation states that maximize the energy difference between cognate and noncognate codon-anticodon interactions. Studies of the interactions between tRNA molecules and their cognate codons in the absence of the ribosome have suggested that triplet-triplet interaction between codon and anticodon is far too weak to account for the specificity of the tRNA selection mechanism during protein synthesis. In contrast, we suggest that such affinity measurements do not adequately describe the interaction between a codon and its cognate tRNA. Thus, such experiments can not detect conformational changes in the tRNA, and, in particular, those stabilized by the ribosome.

Allosteric Regulation↗
PubMedDate not supplied

Na channel kinetics: developing models from non-stationary current fluctuations by analytic methods.

In a previous study, we analyzed Na current fluctuations in myelinated axons from Xenopus laevis under voltage clamp conditions. The statistical properties were analyzed in terms of covariance functions for consecutive time intervals of varying duration during the pulse step. The underlying channel kinetics was analyzed by performing stochastic simulations of published Na channel models and calculating corresponding covariance functions. None of the models explained the fluctuation results. We therefore developed a novel minimal Na channel model that satisfactorily described the results. In the present paper, we extend the analysis and specify the possible models explaining the experimental data by using analytical methods. We derive general relations between the experimental data, including the covariance functions, and the rate constants of specific one-open-state models. A general feature of these models is that they comprise an inactivation step from the first closed state and a relatively low backward rate from the open state. This is in accordance the minimal model inferred from numerical stochastic calculations in the previous study.

Animals↗