Structure of Methylobacterium extorquens malyl‐CoA lyase: CoA‐substrate binding correlates with domain shift

Malyl‐CoA lyase (MCL) is an Mg 2+ ‐dependent enzyme that catalyzes the reversible cleavage of (2 S )‐4‐malyl‐CoA to yield acetyl‐CoA and glyoxylate. MCL enzymes, which are found in a variety of bacteria, are members of the citrate lyase‐like family and are involved in the assimilation of one‐ and two‐carbon compounds. Here, the 1.56 Å resolution X‐ray crystal structure of MCL from Methylobacterium extorquens AM1 with bound Mg 2+ is presented. Structural alignment with the closely related Rhodobacter sphaeroides malyl‐CoA lyase complexed with Mg 2+ , oxalate and CoA allows a detailed analysis of the domain motion of the enzyme caused by substrate binding. Alignment of the structures shows that a simple hinge motion centered on the conserved residues Phe268 and Thr269 moves the C‐terminal domain by about 30° relative to the rest of the molecule. This domain motion positions a conserved aspartate residue located in the C‐terminal domain in the active site of the adjacent monomer, which may serve as a general acid/base in the catalytic mechanism.