Ribonuclease S′ bearing iminodiacetic acid as a metal-binding site was designed and semisynthesized by self-assembly of native S-protein with chemically modified S-peptide. Rationally designed incorporation of unnatural iminodiacetic acid groups as transition metal receptors can confer the dual mode of response to a metal cation (stabilization/destabilization, and thus activation/deactivation) with regard to the structure and activity of an enzyme (see diagram).
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Hamachi et al. (1999) studied this question.