What is it about?

Using insertions and deletions, we switched the coenzyme binding of a protein providing the first evidence of an evolutionary link between distinct chemistries. Historically, protein interactions have been studied using site-directed mutagenesis—a process that gives rise to modified proteins where one or more amino acids are substituted with others. However, until now, researchers have not fully unleashed the potential of “insertions” and “deletions” (collectively referred to as “InDels”). In contrast to amino acid substitutions, an “InDel” significantly modifies protein structure because of the addition or removal of one or more amino acids from the corresponding protein sequence.

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Why is it important?

The structure and function of any protein is coded in its amino acid sequence. It is amazing that the sequence combinations possible for a small protein, about 100 amino acids in length, exceeds the number of atoms in the known universe. For this reason, nature has only explored an infinitesimal fragment of these possibilities, and yet, is able to drive the vast number of reactions that sustain life. Adding InDels to protein engineering protocols could aid the design of artificial enzymes with immense applications.

Perspectives

We engineered an oxidoreductase protein to accept a methylating coenzyme “SAM” instead of its natural coenzyme “NAD.” This involves the redesign of the ancient and highly conserved glycine-rich loop. This task is not trivial because of the complexity of the intramolecular H-bonding and it has attracted the attention of many protein engineers in the past

Saacnicteh Toledo-Patino

Historically, protein interactions have been studied using site-directed mutagenesis—a process that gives rise to modified proteins where one or more amino acids are substituted with others. However, until now, researchers have not fully unleashed the potential of “insertions” and “deletions” (collectively referred to as “InDels”). In contrast to amino acid substitutions, an “InDel” significantly modifies protein structure because of the addition or removal of one or more amino acids from the corresponding protein sequence.

Paola Laurino
Okinawa Institute of Science and Technology Graduate University

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This page is a summary of: Insertions and deletions mediated functional divergence of Rossmann fold enzymes, Proceedings of the National Academy of Sciences, November 2022, Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.2207965119.
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