The importance of the hydrophobic components of the binding energies in the interaction of omega-amino acid ligands with isolated kringle polypeptide domains of human plasminogen.
Three of the five kringle domains of human plasminogen (HPg), viz the first, fourth and fifth, exhibit significantly strong binding to omega-amino acids, such as epsilon-aminocaproic acid (EACA) and transaminomethylcyclohexane-1-carboxylic acid (AMCHA). In all cases, ligand stabilization is due to ion dipole attractions of its charged groups with polypeptide side chains, as well as hydrophobic clustering of the ligand methylene groups with appropriate hydrophobic residues within the kringle domain. In order to estimate the significance of the hydrophobic components of ligand stabilization, we have sought a more detailed description of these binding interactions. The standard thermodynamic binding parameters, delta G degrees, delta H degrees and delta S degrees, for association of EACA and AMCHA with isolated recombinant kringle regions of HPg have been determined at several temperatures to evaluate the changes in standard heat capacities (delta C degrees p) accompanying these interactions. In each case, the delta C degrees p values of binding were negative and in the range -36 to -91 cal mol -1 K -1, reflective of the importance of the hydrophobic components of the binding process and their probable effects on surrounding water structure.
Menhart
N
N
Department of Chemistry and Biochemistry, University of Notre Dame, Indiana, USA.
Castellino
F J
FJ
D000596:Amino Acids / Q000378:metabolism*; D004734:Energy Metabolism; D006801:Humans; D018082:Kringles; D008024:Ligands; D010958:Plasminogen / Q000378:metabolism*; D011485:Protein Binding; D011994:Recombinant Proteins / Q000378:metabolism
D000596:Amino Acids; D008024:Ligands; D011994:Recombinant Proteins; D010958:Plasminogen