Thermodynamics of metal ion binding. 1. Metal ion binding by wild-type carbonic anhydrase.
Understanding the energetic consequences of molecular structure in aqueous solution is a prerequisite to the rational design of synthetic motifs with predictable properties. Such properties include ligand binding and the collapse of polymer chains into discrete three-dimensional structures. Despite advances in macromolecular structure determination, correlations of structure with high-resolution thermodynamic data remain limited. Here we compare thermodynamic parameters for the binding of Zn(II), Cu(II), and Co(II) to human carbonic anhydrase II. These calorimetrically determined values are interpreted in terms of high-resolution X-ray crystallographic data. While both zinc and cobalt are bound with a 1:1 stoichiometry, CAII binds two copper ions. Considering only the high-affinity site, there is a diminution in the enthalpy of binding through the series Co(II) --> Zn(II) --> Cu(II) that mirrors the enthalpy of hydration; this observation reinforces the notion that the thermodynamics of solute association with water is at least as important as the thermodynamics of solute-solute interaction and that these effects must be considered when interpreting association in aqueous solution. Additionally, DeltaC(p) data suggest that zinc binding to CAII proceeds with a greater contribution from desolvation than does binding of either copper or cobalt, suggesting Nature optimizes binding by optimizing desolvation.
DiTusa
C A
CA
Department of Chemistry, Duke University, Durham, North Carolina 27708, USA.
Christensen
T
T
McCall
K A
KA
Fierke
C A
CA
Toone
E J
EJ
D001051:Apoenzymes / Q000737:chemistry; D001665:Binding Sites; D002021:Buffers; D002151:Calorimetry; D002256:Carbonic Anhydrases / Q000737:chemistry*; D002413:Cations, Divalent / Q000737:chemistry; D003035:Cobalt / Q000737:chemistry; D003300:Copper / Q000737:chemistry; D020035:Holoenzymes / Q000737:chemistry; D006801:Humans; D008024:Ligands; D008670:Metals / Q000737:chemistry*; D011522:Protons; D013816:Thermodynamics; D019287:Zinc Sulfate / Q000737:chemistry
D001051:Apoenzymes; D002021:Buffers; D002413:Cations, Divalent; D020035:Holoenzymes; D008024:Ligands; D008670:Metals; D011522:Protons; D003035:Cobalt; D019287:Zinc Sulfate; D003300:Copper; D002256:Carbonic Anhydrases