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S B Easterbrook-Smith

Publications and source records attributed to S B Easterbrook-Smith.

47 records · Page 3Linked to original sources
PubMed1982

A reinterpretation of the evidence for an interaction between Clq and pairs of immunoglobulin molecules in an immune lattice.

An error in a previous article [Cohen S. (1968) J. Immun. 100, 407-413] was discovered which invalidates it as evidence that IgG immune complexes activate the classical complement pathway by an interaction involving pairs of antibody molecules, so-called doublet formation. The error concerns the correction to be made for the observed 8% residual activity of the modified antibody preparation used. When appropriate correction factors are applied, the data are found not to be consistent with the hypothesis of doublet formation. The analysis presented here has no bearing on the original article's experimental techniques, nor on its demonstration of co-operation between IgG molecules during complement fixation.

Antigen-Antibody Complex↗
PubMed1980

The Clq receptor site on immunoglobulin G.

We propose that, the binding site for the complement subcomponent Clq on immunoglobulin G involves the last two (C-terminal) beta-strands of the C gamma 2 domain. This region contains a large number of accessible and highly conserved charged residues and charge is postulated as an important component of the Clq-IgG interaction. The conclusions are reached on the basis of accessibility and sequence conservation analyses of C gamma 2 amino acid residues, the use of specific inhibitors and chemical modification studies.

Amino Acid Sequence↗
PubMed1979

The atypical velocity response by pyruvate carboxylase to increasing concentrations of acetyl-coenzyme A.

An investigation was made of the interaction of pyruvate carboxylase with its allosteric effector, acetyl-CoA, and the velocity profile of the deacylation of acetyl-CoA as a function of acetyl-CoA concentration indicated that this ligand does not bind to this enzyme in a positive homotropic co-operative manner. An examination was therefore made of the factors that contribute to the sigmoidicity of the rate curves obtained for pyruvate carboxylation with various concentrations of acetyl-CoA. Hill coefficients for acetyl-CoA obtained with both sheep and chicken liver pyruvate carboxylases were found to be dependent on the fixed pyruvate concentration used in the assay solution. Thus, by varying the acetyl-CoA concentration, the degree of saturation of the enzyme by pyruvate was also changed. A further consequence of non-saturating concentrations of pyruvate was that the non-productive hydrolysis of the enzyme- carboxybiotin complex increased, resulting in an under-estimate of the reaction velocity measured by oxaloacetate formation. Another factor contributing to the sigmoidicity is that, at non-saturating concentrations of acetyl-CoA, the enzyme undergoes inactivation upon dilution to low protein concentrations, again resulting in an under-estimate of the reaction velocity. Under conditions where none of the above factors was operating and the only effect of varying acetyl-CoA concentrations was to alter the proportion of the enzyme catalysing the carboxylation reaction at acetyl-CoA-dependent and -independent rates, the sigmoidicity of the acetyl-CoA velocity profile was completely eliminated.

Acetyl Coenzyme A↗
PubMed1978

A reappraisal of the reaction pathway of pyruvate carboxylase.

The reaction pathway catalysed by pyruvate carboxylase was re-examined by using two independent experimental approaches not previously applied to this enzyme. To avoid the variable stoicheiometry associated with oxaloacetate formation, the reaction rate was measured by following release of Pi. Initial velocities, when plotted as a function of varying concentrations of either MgATP2- or HCO3-, at fixed concentrations of pyruvate, gave in double-reciprocal-form families of straight intersecting lines. Further, when the reaction velocity was determined as a function of varying MgATP2- concentrations by using pyruvate, 3-fluoropyruvate and 2-oxobutyrate as alternative carboxyl-acceptor substrates, the slopes of the double-reciprocal plots were significantly different. Both results support a sequential reaction pathway.

Adenosine Triphosphate↗
PubMed1976

Pyruvate carboxylase: affinity labelling of the magnesium adenosine triphosphate binding site.

The 2' , 3'-dialdehyde derivative of ATP (oATP) was prepared by periodate oxidation and on the following criteria was considered to be an effective affinity label. The magnesium complex of this derivative (Mg-oATP2) was shown to ba linear competitive inhibitor with respect to MgATP2-in both the acetyl-CoA-dependent and -independent activities of the enzyme but was a non-competitive inhibitor with respect to bicarbonate, and an uncompetitive inhibitor with respect to pyruvate. Mg-oATP was covalently bound to pyruvate carboxylase by reduction using sodium borohydride with concurrent irreversible inactivation of the enzyme...

Acetyl Coenzyme A↗