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Cooperative cyclic interactions involved in metal binding to pairs of sites in EF‐hand proteins
Author(s) -
Biekofsky Rodolfo R,
Feeney James
Publication year - 1998
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(98)01349-0
Subject(s) - cooperativity , cooperative binding , chemistry , metal , hydrogen bond , crystallography , amide , binding energy , acceptor , metal ions in aqueous solution , calmodulin , binding site , stereochemistry , molecule , enzyme , atomic physics , biochemistry , physics , organic chemistry , condensed matter physics
This study focuses on a closed net of electron‐pair donor–acceptor interactions, present in the core of all metal‐bound EF‐hand pairs, that link both metal ions across a short two‐stranded β‐sheet. A molecular model based on the above cycle of interactions was studied using semi‐empirical molecular orbital quantum mechanical methods. The calculations indicate that the interactions in the model cycle are cooperative, that is, that the interaction energy of the cyclic structure is greater than that of the sum of isolated interactions between its components. The cooperativity in this cycle can be attributed to an increase in the stability of the interactions resulting from a mutual polarisation of the associated groups. The predicted polarisation of the amide groups in the cycle is in agreement with experimental NMR 15 N deshielding observed for these amide groups upon metal binding. Experimental observations of strengthening of the β‐sheet hydrogen bonds are also consistent with the model calculations. By this mechanism, the binding of the first metal ion would enhance the binding of the second metal ion, and thus, the intradomain cooperativity in cation binding of calmodulin and related EF‐hand proteins can be ascribed, at least partly, to this short‐range molecular mechanism.