The capture and conversion of atmospheric CO2 remain challenging for chemistry, resulting in an ever-increasing interest to understand and exploit CO2-fixation mechanisms. Enoyl-CoA carboxylases/reductases (ECRs) are the most efficient CO2-fixing enzymes found in nature to date, outcompeting RuBisCO (the key enzyme in photosynthesis) in activity by more than an order of magnitude. However, the molecular mechanisms underlying ECR’s extraordinary catalytic activity remain elusive. In a large consortium that included Tobias Erb (Max Planck Institute for Terrestrial Microbiology) and scientists at the U.S. Department of Energy’s (DOE) SLAC National Accelerator Laboratory (SLAC) and the DOE Joint Genome Institute, multiple crystallographic approaches were used, including synchrotron and X-ray free electron laser (XFEL) experiments, to study the fixation mechanism of ECR from Kitasatospora setae. The researchers used the Stanford Synchrotron Radiation Lightsource (SSRL) beamline 12-2 to collect data from a ternary structure containing ECR and bound butyryl-CoA and NADPH. The complex formed a tetramer organized as a dimer of dimers with both “open” and “closed” states with respect to the active site. Dimer subunits are stabilized with the binding of NADPH. Two of these subunits, one open and one closed, form the overall dimer. This tetramer that differentiates into a dimer of dimers of open- and closed-form subunits suggests that the enzyme operates with “half-site reactivity” and in conformational synchrony to achieve the observed high catalytic rates.
DeMirci, H., et al. 2019. “Coupled Inter-Subunit Dynamics Enable the Fastest CO2-Fixation by Reductive Carboxylases,” bioRxiv preprint. [DOI:10.1101/607101].