title: Hydration of carbon dioxide by carbonic anhydrase: internal proton transfer of Zn2+-bound HCO3-.
abstract: Proton transfer within HCO3- has been examined under various conditions through molecular orbital methods: partial retention of diatomic differential overlap and 4-31G self-consistent field programs. These conditions include the absence or presence of Zn2+, Zn2+(NH3)3, or a water ligand on Zn2+. In addition, 4-31G+ and some MP2/4-31G results are obtained. The use of Be2+ to simulate Zn2+ reproduces reaction pathways and energy barriers, except for marginal cases. The barrier of 35.6 kcal/mol for direct internal proton transfer is reduced to 3.5 kcal/mol when one water molecule, not bound to Zn2+, is included for proton relay and to 1.4 kcal/mol when two such water molecules are included. In the enzyme, either Thr-199 or solvent molecules could perform this relay function. Our results favor this facilitated proton transfer over a mechanism in which Zn2+-bound OH- attacks CO2, a bidentate intermediate forms, and the OH moiety of the resulting HCO3- dissociates from Zn2+, thus leaving one of the oxygens of the original CO2 as a ligand to Zn2+.
authors.affiliation: Gibbs Chemical Laboratories, Department of Chemistry, Harvard University, Cambridge, Massachusetts 02138.
authors.forename: J Y
authors.initials: JY
authors.lastname: Liang
authors.forename: W N
authors.initials: WN
authors.lastname: Lipscomb
mesh_terms: D001639:Bicarbonates / Q000378:metabolism*; D002151:Calorimetry; D002245:Carbon Dioxide / Q000378:metabolism*; D002256:Carbonic Anhydrases / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D011485:Protein Binding; D011522:Protons; D015032:Zinc / Q000378:metabolism*
chemical_list: D001639:Bicarbonates; D011522:Protons; D002245:Carbon Dioxide; D002256:Carbonic Anhydrases; D015032:Zinc