title: An electrostatic model for the interaction between growth hormone and its receptor involving chelation of Ca2+ to the human growth hormone molecule.
abstract: We previously postulated the local involvement of cations in the complex between human growth hormone and its receptors in the liver. The original electrostatic model involved convergence of unit negative charges on the hormone and receptor, towards an interposed Ca2+ ion. That model was consistent with (a) the Ca2+ dependence of human growth hormone binding, (b) the magnitude of the Ca2+ mediated increase in the affinity of human growth hormone binding, and (c) could also explain the relative affinities of human and non-primate growth hormones for growth hormone receptors. In the present report, the original electrostatic model is revised with the postulate that Ca2+ is chelated to the human growth hormone molecule. The consequences of this postulate are explored mathematically with the result that it becomes necessary to propose an additional unique hindrance determinant (positive residues in helices one and four are good candidates) to account for the lower affinity of non-primate growth hormones relative to human growth hormone. Predictions are made regarding the effect of a particular point mutation (at position 34) on the affinity of hormone binding.
authors.affiliation: Department of Physiology and Pharmacology, University of Queensland, Australia.
authors.forename: R
authors.initials: R
authors.lastname: Barnard
authors.forename: S W
authors.initials: SW
authors.lastname: Rowlinson
authors.forename: M J
authors.initials: MJ
authors.lastname: Waters
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002614:Chelating Agents; D004563:Electrochemistry; D013006:Growth Hormone / Q000378:metabolism*; D006801:Humans; D008433:Mathematics; D008956:Models, Chemical; D009154:Mutation; D011986:Receptors, Somatotropin / Q000378:metabolism*
chemical_list: D002614:Chelating Agents; D011986:Receptors, Somatotropin; D013006:Growth Hormone; D002118:Calcium