Biomedical subjects

C H Robert

Publications and source records attributed to C H Robert.

21 records · Page 2Linked to original sources

PubMed1987

Nesting: hierarchies of allosteric interactions.

A generalization of the allosteric model is presented that incorporates a hierarchy of conformational equilibria. Such a formulation draws upon structural organization already seen in many large macromolecular systems. The functional binding properties of the macromolecule reflect conformational equilibria at each structural level. Appropriate "nested" models are used to interpret structural features and functional aspects of two hemocyanin systems with a large number (12 and 24) of binding sites.

Allosteric Regulation↗

PubMed1986

Analysis of zeros of binding polynomials for tetrameric hemoglobins.

A quantitative measure of the validity of the MWC description of cooperative binding equilibria has been obtained which uses only the Adair constants. This is accomplished through simple relationships using the zeros of the Adair binding polynomial and unique properties of the zeros of MWC polynomials as described in the accompanying paper (W.E. Briggs, Biophys. Chem. 24 (1986) 311). The method is applied to oxygen binding to a large number of hemoglobins under a wide variety of conditions. In most cases, exemplified by human hemoglobin under a wide range of conditions, the MWC model is allowed and the probability of its suitability is determined. The probability given by this method correlates directly with the deviation between the experimental binding curve and that derived from the theory. In several cases the pattern of the Adair polynomial zeros immediately excludes the MWC model, most notably for carp hemoglobins. A physical picture of cooperative binding site interactions is nevertheless obtained from the patterns of zeros as they relate to the factorization of the binding polynomial.

Animals↗

PubMed1986

Cooperative free energies for nested allosteric models as applied to human hemoglobin.

A model is developed for ligand binding to human hemoglobin that describes the detailed cooperative free-energies for each of the ten different ligated (cyanomet) species as observed by Smith and Ackers (Smith, F.R., and G.K. Ackers. 1985. Proc. Natl. Acad. Sci. USA.82:5347-5351). The approach taken here is an application of the general principle of hierarchical levels of allosteric control, or nesting, as suggested by Wyman (Wyman, J. 1972. Curr. Top. Cell. Reg. 6:207-223). The model is an extension of the simple two-state MWC model (Monod, J., J. Wyman, and J.P. Changeux. 1965. J. Mol. Biol. 12:88-118) using the idea of cooperative binding within the T (deoxy) form of the macromolecule, and has recently been described as a "cooperon" model (Di Cera, E. 1985. Ph.D. thesis). The T-state cooperative binding is described using simple interaction rules first devised by Pauling (Pauling, L. 1935. Proc. Natl. Acad. Sci. USA. 21:186-191). In this application three parameters suffice to describe the cooperative free-energies of the 10 ligated species of cyanomet hemoglobin. The redox process in the presence of cyanide, represented as a Hill plot, is simulated from Smith and Ackers' cooperative free-energies and is compared with available electrochemical binding measurements.

Allosteric Regulation↗