This laboratory is interested in the relationshipbetween protein sequence, structure and the mechanisms of protein folding and enzymic reactions.(i) Histidine Rich Proteins We are reinvestigating the spectroscopic behaviour of poly L-histidine as a function of pH and solvent additives, in an effort to establish a set of reference circular dichroism spectra (CD) under defined conditions, which can be used in analysis of the structures of unusual proteins, produced by malaria parasites. The polypeptides CD spectrum is found to be a complex function of pH and solvent composition which is most easily interpreted by assuming the presence of different forms with unique molecular conformations.(ii) Structure of Tryptophan Synthase (with Dr. Edith Wilson Miles and coworkers, LBP) We are investigating the conformational states of the tryptophan synthase alpha2-beta2 complex and their relevance in the enzymatic mechanism of the protein.(iii) Structure of Mammalian Sulphotransferases. (with Dr. D. Marshall and Dr. W.B. Jakoby, LBM) The enzymatic activity of a phenol sulphotransferase, from rat liver, has been shown to be regulated by reversible oxidation/reduction of a conserved specific cysteine residue by physiological concentrations of glutathione. Oxdation cysteine residue 66 inhibits thephysiological activity of the enzyme by very tight substrate inhibition. This mechanism may be important under conditions of oxidative stress to the liver.(iv) Interaction of Neurogranin with Calmodulin. (with Dr. K.P. Huang, ERRB, NICHD) In the absence of calcium, neurorgranin forms an inactive complex with calmodulin, which can be detected by anincrease in alpha-helical conent of the proteins. The formation of the complex can be regulated by variations in calcium ion concentrations or by oxidation/reduction of a pair of conservedcysteine residues in neurogranin. (v) Structure and Interactions of Proline rich Proteins from Human Saliva (with Dr. R. I. Henkin, Georgetown University). We are studying the effects of sovent additives and other proteins on the CD spectra of physiologically important proteins isolated from saliva. - protein, structure, function, folding, spectroscopy, circular-dichroism, thermodynamics, kinetics.
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