Probing anion recognition in a cobalt(II) de novo designed metalloprotein
Salvatore La Gatta1, Jacob K Firby1, James E Penner-Hahn2
1Department of Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.
Journal of Inorganic Biochemistry
|February 19, 2026
Summary
Designed protein scaffolds with cobalt(II) centers bind anions like thiocyanate with millimolar affinity. This binding changes the cobalt(II) geometry, offering insights into metalloprotein design for substrate activation.
Area of Science:
- Protein engineering and design
- Bioinorganic chemistry
- Coordination chemistry
Background:
- Anions influence metal-site structure and function.
- De novo designed metallocoiled coils provide a platform to study anion recognition.
- Artificial carbonic anhydrases (CA) serve as models for zinc(II) centers.
Purpose of the Study:
- Investigate anion binding to a designed three-stranded coiled coil (3SCC) scaffold.
- Determine the binding affinities and spectral changes associated with anion recognition.
- Elucidate the structural and geometric consequences of anion binding to a cobalt(II)(His)3 site.
Main Methods:
- Spectroscopic examination (visible and X-ray absorption spectroscopy) of anion binding.
- Utilized de novo designed GRW-H peptide scaffolds with cobalt(II) substitution.
- Performed pH-dependent binding studies.
Main Results:
- Nitrite, azide, and thiocyanate bind to the cobalt(II)(His)3 site with millimolar affinities.
- Thiocyanate binding induces a change from octahedral to five-coordinate cobalt(II) geometry.
- Anion binding affinity is influenced by solution pH, with increased affinity at higher pH.
- Halides bind significantly weaker than pseudohalides.
Conclusions:
- The His3 site in the designed protein scaffold recognizes anions and adopts distinct cobalt(II) geometries.
- Protein residue deprotonation likely strengthens thiocyanate binding.
- These findings provide a foundation for designing metalloproteins for small inorganic substrate activation.
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