title: Carboxylate binding modes in zinc proteins: a theoretical study.
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, approximately 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.
authors.affiliation: Department of Theoretical Chemistry, Chemical Centre, Lund University, S-221 00 Lund, Sweden. ulf.ryde@teokem.lu.se
authors.forename: U
authors.initials: U
authors.lastname: Ryde
mesh_terms: D002264:Carboxylic Acids / Q000737:chemistry / Q000378:metabolism*; D002268:Carboxypeptidases / Q000737:chemistry / Q000378:metabolism; D006878:Hydroxides / Q000378:metabolism; D008024:Ligands; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D011522:Protons; D011789:Quantum Theory; D013237:Stereoisomerism; D013820:Thermolysin / Q000737:chemistry / Q000378:metabolism; D014867:Water / Q000378:metabolism; D015032:Zinc
chemical_list: D002264:Carboxylic Acids; D006878:Hydroxides; D008024:Ligands; D011506:Proteins; D011522:Protons; D014867:Water; D002268:Carboxypeptidases; D013820:Thermolysin; D015032:Zinc