DERA Human

DERA catalyzes the reversible chemical reaction:

$$2-deoxy-D-ribose 5-phosphate \rightleftharpoons D-glyceraldehyde 3-phosphate + acetaldehyde$$

The enzyme operates via the formation of a Schiff base with Lys 167 at the active site. Lys 201 is critical for the reaction as it increases the acidity of protonated Lys 167, facilitating Schiff base formation. DERA exhibits some substrate promiscuity, accepting various carbonyl compounds as substrates. The aldol reaction is stereospecific, giving the (S)-configuration at the reactive carbon .

DERA is a Class I aldolase and contains a TIM α/β barrel fold. The enzyme is found in homodimers or homotetramers, which increases its thermal stability through hydrophobic interactions and hydrogen bonding between interfacial residues. In humans, DERA is mainly expressed in the lungs, liver, and colon and is necessary for the cellular stress response .

DERA is utilized in organic synthesis for its ability to catalyze stereoselective C–C bond formation between acetaldehyde and other aldehydes. However, its practical application is limited by its poor tolerance towards industrially relevant concentrations of aldehydes, particularly acetaldehyde. To overcome this, protein engineering and immobilization on appropriate supports are employed to enhance its aldehyde resistance .

Research has shown that DERA can be used to catalyze the backward aldol reaction, and it has been found to accept a variety of aldehydes in place of D-glyceraldehyde 3-phosphate. Molecular modeling of the active site has revealed a hydrophilic pocket formed by Thr 170 and Lys 172 to stabilize the C2-hydroxy group of D-glyceraldehyde 3-phosphate .