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

JAVIER MARCELO GONZALEZ; RICARDO MARTI-ARBONA; JULIAN CHEN; CLIFF UNKEFER

ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY AND CRYSTALLIZATION COMMUNICATIONS

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2017 vol. F73 p. 79 - 85

1744-3091

Malyl-CoA lyase (MCL) is an Mg2+-dependent enzyme that catalyzes thereversible cleavage of (2S)-4-malyl-CoA to yield acetyl-CoA and glyoxylate.MCL enzymes, which are found in a variety of bacteria, are members of thecitrate lyase-like family and are involved in the assimilation of one- and two carboncompounds. Here, the 1.56 A resolution X-ray crystal structure of MCLfrom Methylobacterium extorquens AM1 with bound Mg2+ is presented.Structural alignment with the closely related Rhodobacter sphaeroides malyl-CoA lyase complexed with Mg2+, oxalate and CoA allows a detailed analysis ofthe domain motion of the enzyme caused by substrate binding. Alignment of thestructures shows that a simple hinge motion centered on the conserved residuesPhe268 and Thr269 moves the C-terminal domain by about 30 relative to therest of the molecule. This domain motion positions a conserved aspartateresidue located in the C-terminal domain in the active site of the adjacentmonomer, which may serve as a general acid/base in the catalytic mechanism.