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Thermodynamics of metal ion binding. 2. Metal ion binding by carbonic anhydrase variants.

Publication ,  Journal Article
DiTusa, CA; McCall, KA; Christensen, T; Mahapatro, M; Fierke, CA; Toone, EJ
Published in: Biochemistry
May 2001

The ability to construct molecular motifs with predictable properties in aqueous solution requires an extensive knowledge of the relationships between structure and energetics. The design of metal binding motifs is currently an area of intense interest in the bioorganic community. To date synthetic motifs designed to bind metal ions lack the remarkable affinities observed in biological systems. To better understand the structural basis of metal ion affinity, we report here the thermodynamics of binding of divalent zinc ions to wild-type and mutant carbonic anhydrases and the interpretation of these parameters in terms of structure. Mutations were made both to the direct His ligand at position 94 and to indirect, or second-shell, ligands Gln-92, Glu-117, and Thr-199. The thermodynamics of ligand binding by several mutant proteins is complicated by the development of a second zinc binding site on mutation; such effects must be considered carefully in the interpretation of thermodynamic data. In all instances modification of the protein produces a complex series of changes in both the enthalpy and entropy of ligand binding. In most cases these effects are most readily rationalized in terms of ligand and protein desolvation, rather than in terms of changes in the direct interactions of ligand and protein. Alteration of second-shell ligands, thought to function primarily by orienting the direct ligands, produces profoundly different effects on the enthalpy of binding, depending on the nature of the residue. These results suggest a range of activities for these ligands, contributing both enthalpic and entropic effects to the overall thermodynamics of binding. Together, our results demonstrate the importance of understanding relationships between structure and hydration in the construction of novel ligands and biological polymers.

Duke Scholars

Published In

Biochemistry

DOI

EISSN

1520-4995

ISSN

0006-2960

Publication Date

May 2001

Volume

40

Issue

18

Start / End Page

5345 / 5351

Related Subject Headings

  • Zinc
  • Thermodynamics
  • Protein Binding
  • Mutagenesis, Site-Directed
  • Ligands
  • Hydrogen Bonding
  • Humans
  • Histidine
  • Glutamine
  • Glutamic Acid
 

Citation

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DiTusa, C. A., McCall, K. A., Christensen, T., Mahapatro, M., Fierke, C. A., & Toone, E. J. (2001). Thermodynamics of metal ion binding. 2. Metal ion binding by carbonic anhydrase variants. Biochemistry, 40(18), 5345–5351. https://doi.org/10.1021/bi0017327
DiTusa, C. A., K. A. McCall, T. Christensen, M. Mahapatro, C. A. Fierke, and E. J. Toone. “Thermodynamics of metal ion binding. 2. Metal ion binding by carbonic anhydrase variants.Biochemistry 40, no. 18 (May 2001): 5345–51. https://doi.org/10.1021/bi0017327.
DiTusa CA, McCall KA, Christensen T, Mahapatro M, Fierke CA, Toone EJ. Thermodynamics of metal ion binding. 2. Metal ion binding by carbonic anhydrase variants. Biochemistry. 2001 May;40(18):5345–51.
DiTusa, C. A., et al. “Thermodynamics of metal ion binding. 2. Metal ion binding by carbonic anhydrase variants.Biochemistry, vol. 40, no. 18, May 2001, pp. 5345–51. Epmc, doi:10.1021/bi0017327.
DiTusa CA, McCall KA, Christensen T, Mahapatro M, Fierke CA, Toone EJ. Thermodynamics of metal ion binding. 2. Metal ion binding by carbonic anhydrase variants. Biochemistry. 2001 May;40(18):5345–5351.
Journal cover image

Published In

Biochemistry

DOI

EISSN

1520-4995

ISSN

0006-2960

Publication Date

May 2001

Volume

40

Issue

18

Start / End Page

5345 / 5351

Related Subject Headings

  • Zinc
  • Thermodynamics
  • Protein Binding
  • Mutagenesis, Site-Directed
  • Ligands
  • Hydrogen Bonding
  • Humans
  • Histidine
  • Glutamine
  • Glutamic Acid