Carboxylate binding modes in zinc proteins: A theoretical study

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift


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.


Enheter & grupper

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Teoretisk kemi
Sidor (från-till)2777-2787
Antal sidor11
TidskriftBiophysical Journal
Utgåva nummer5
StatusPublished - 1999 nov
Peer review utfördJa