Carboxylate binding modes in zinc proteins: A theoretical study
Research output: Contribution to journal › Article
Abstract
The relative energies of different coordination modes (bidentate, monodentate, syn, and anti) of a carboxylate group bound to a zinc ion have been studied by the density functional method B3LYP with large basis sets on realistic models of the active site of several zinc proteins. In positively charged four-coordinate complexes, the mono- and bidentate coordination modes have almost the same energy (within 10 kJ/mol). However, if there are negatively charged ligands other than the carboxylate group, the monodentate binding mode is favored. In general, the energy difference between monodentate and bidentate coordination is small, 4-24 kJ/mol, and it is determined more by hydrogen-bond interactions with other ligands or second- sphere groups than by the zinc-carboxylate interaction. Similarly, the activation energy for the conversion between the two coordination modes is small, ~6 kJ/mol, indicating a very flat Zn-O potential surface. The energy difference between syn and anti binding modes of the monodentate carboxylate group is larger, 70-100 kJ/mol, but this figure again strongly depends on interactions with second-sphere molecules. Our results also indicate that the pK(a) of the zinc-bound water ligand in carboxypeptidase and thermolysin is 8-9.
Details
Authors | |
---|---|
Organisations | |
Research areas and keywords | Subject classification (UKÄ) – MANDATORY
|
Original language | English |
---|---|
Pages (from-to) | 2777-2787 |
Number of pages | 11 |
Journal | Biophysical Journal |
Volume | 77 |
Issue number | 5 |
Publication status | Published - 1999 Nov |
Publication category | Research |
Peer-reviewed | Yes |