THE SCIENCE
How enzymatic deglycation works — six steps
The reported CMLase reaction is precise: it recognises one specific modification and reverses it, leaving the rest of the protein untouched. Each step below can be opened for detail.
CMLase does not replace the entire protein. It acts on a specific chemical modification located on the protein.
Lysine becomes CML
A lysine residue on a long-lived protein reacts non-enzymatically and is converted into Nε-carboxymethyl-lysine. The modification is stable: under ordinary physiological conditions it does not revert on its own.
CMLase recognises the CML side chain
The engineered enzyme binds the modified side chain. Recognition — distinguishing CML from the thousands of ordinary lysine residues around it — is the core achievement of the computational design and directed-evolution work behind CrGO-897.
The active site positions the modification for oxidation
Within the engineered active site, the carboxymethyl group is positioned for an oxidative reaction, using the chemistry of the glycine-oxidase scaffold from which the enzyme was developed.
The carboxymethyl group is processed
The modification is oxidatively processed and cleaved from the lysine side chain — the chemical step that no natural enzyme was known to perform on protein-bound CML.
Lysine is restored
The affected residue is returned to lysine. The protein itself is not replaced or rebuilt — one specific chemical mark on it has been removed.
Glyoxylate and hydrogen peroxide are generated
The reaction produces glyoxylate and hydrogen peroxide as by-products. Managing these products — particularly peroxide — is one of the formulation and delivery questions the Panacea research programme investigates.