HOW NONBONDING AMINO-ACID SIDE-CHAINS MAY ENORMOUSLY INCREASE THE STABILITY OF A CU(II)-PEPTIDE COMPLEX

A combined pH-metric and spectroscopic (W-Vis, circular dichroism and electron paramagnetic resonance) study of Cu(II) binding to analogues of Asn-Ser-Phe-Arg-Tyr-NH2 systematically substituted with Ala residue s revealed the presence of indirect, additive conformational effects r esulting in a very high stability enhancement for 4N complexes. The ma jor contribution to the stability is exerted by nonbinding side-chains of 4th and 5th amino acids. This effect is explained on the basis of spectroscopic data by the formation of a secondary fence shielding the Cu(II) binding site from the bulk of the solution. Such a structure, not reported previously, is of possible importance for the understandi ng of interactions of metal ions with proteins. (C) 1998 Elsevier Scie nce S.A. All rights reserved.