Coordination chemistry within a protein host: regulation of the secondary coordination sphere

Abstract

Secondary coordination spheres of metal complexes are instrumental in controlling properties that are linked to function. To study these effects in aqueous solutions artificial Cu proteins have been developed using biotin–streptavidin (Sav) technology and their binding of external azide ions investigated. Parallel binding studies were done in crystallo on single crystals of the artificial Cu proteins. Spectroscopic changes in solution are consistent with azide binding to the Cu centers. Structural studies corroborate that a Cu–N3 unit is present in each Sav subunit and reveal the composition of hydrogen bonding (H-bonding) networks that include the coordinated azido ligand. The networks involve amino acid residues and water molecules within the secondary coordination sphere. Mutation of these residues to ones that cannot form H-bonds caused a measurble change in the equilibrium binding constants that were measured in solution. These findings further demonstrate the utility of biotin–Sav technology to prepare water-stable inorganic complexes whose structures can be controlled within both primary and secondary coordination spheres.

A guide to secondary coordination sphere editing

“…This tutorial considers molecular coordination compounds only, though artificial metalloproteins have also been used to manipulate SCS environments. [1][2][3] 2. Hydrogen bond acceptors…”

De novodesigned coiled coils as scaffolds for lanthanides, including novel imaging agents with a twist

“…Further work by Hodges and co-workers showed that the stabilising effect of La 3+ addition on their coiled coils was highly dependent on the position of the Gln to Glu substitutions. 112 Three peptides were made, (E 2 (15,20), E 2 (13,22) and E 2 (20,22), Table 1), with varying distances between the two repulsive Glu e and g residues. Addition of LaCl 3 had a greater stabilising effect on E 2 (15,20) coiled coil formation than for E 2 (13,22), reflecting the reduction in the magnitude of Glu-Glu repulsion as the distance between them increases.…”

“…112 Three peptides were made, (E 2 (15,20), E 2 (13,22) and E 2 (20,22), Table 1), with varying distances between the two repulsive Glu e and g residues. Addition of LaCl 3 had a greater stabilising effect on E 2 (15,20) coiled coil formation than for E 2 (13,22), reflecting the reduction in the magnitude of Glu-Glu repulsion as the distance between them increases. Whilst, of the three peptides, the Glu residues are physically closest in the E 2 (20,22) Hydrophobic residues are black and salt bridge interactions between g and e residues are shown (red).…”

“…In the two stranded coiled coil, this bulky Leu side chain protrudes into the interhelical interface between the two Glu residues of the two peptide chains, interfering with the repulsive interaction between the two Glu residues, thus reducing relief provided by La 3+ binding. Substitution of a third Glu in place of a Gln residue in the E 2 (15,20) peptide to give E (13,15,20) and E (15,20,22) (Table 1) resulted in enhanced coiled coil stability on addition of trivalent La 3+ regardless of whether the third Glu was in position 13 or 22. The resulting charge neutrality provides additional stabilisation, even if direct lanthanide coordination to all three Glu residues is not possible.…”

“…8 Proteins act as sophisticated ligands which are able to precisely control metal coordination chemistry, thereby tuning protein function. [9][10][11][12][13] Thus harnessing the power of proteins as ligands for metal ions is an attractive prospect and an active area of research. [14][15][16][17][18][19] One strategy is the design of structured peptides de novo, whereby miniaturized scaffolds with metal-binding sites that replicate the environment found within more complex proteins are engineered.…”