An artificial metallolyase with pliable 2-His-1-carboxylate facial triad for stereoselective Michael addition

We repurposed the metal-binding site of a cupin superfamily protein into the 2-His-1-carboxylate facial triad, which is one of the common motifs in natural non-heme enzymes, to construct artificial metalloenzymes that can catalyze new-to-nature reactions. The Cu2+-H52A/H58E variant catalyzed the stereoselective Michael addition reaction and was found to bear a flexible metal-binding site in the high-resolution crystal structure. Furthermore, the H52A/H58E/F104W mutant accommodated a water molecule, which was supported by Glu58 and Trp104 residues via hydrogen bonding, presumably leading to high stereoselectivity. Thus, the 2-His-1-carboxylate facial triad was confirmed to be a versatile and promising metal-binding motif for abiological and canonical biological reactions.

• Publication year

  2023

• Venue

  Chemical Science

• Publication date

  2023-03-13

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1039/d2sc06809ePMID 37035687PMCID 10074404
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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