TY - JOUR T1 - Coupled inter-subunit dynamics enable the fastest CO<sub>2</sub>-fixation by reductive carboxylases JF - bioRxiv DO - 10.1101/607101 SP - 607101 AU - Hasan DeMirci AU - Yash Rao AU - Gabriele M. Stoffel AU - Bastian Vögeli AU - Kristina Schell AU - Alexander Batyuk AU - Cornelius Gati AU - Raymond G. Sierra AU - Mark S. Hunter AU - E. Han Dao AU - Halil I. Ciftci AU - Brandon Hayes AU - Fredric Poitevin AU - Kensuke Tono AU - David Adrian Saez AU - Esteban Vöhringer-Martinez AU - Samuel Deutsch AU - Yasuo Yoshikuni AU - Tobias J. Erb AU - Soichi Wakatsuki Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/04/12/607101.abstract N2 - Enoyl-CoA carboxylases/reductases (ECRs) are the most efficient CO2-fixing enzymes described to date, outcompeting RubisCO, the key enzyme in photosynthesis in catalytic activity by more than an order of magnitude. However, the molecular mechanisms underlying ECR’s extraordinary catalytic activity remain elusive. Here we used different crystallographic approaches, including ambient temperature X-ray Free Electron Laser (XFEL) experiments, to study the dynamic structural organization of the ECR from Kitasatospora setae. K. setae ECR is a homotetramer that differentiates into a dimer of dimers of open- and closed-form subunits in the catalytically active state, suggesting that the enzyme operates with “half-site reactivity” to achieve high catalytic rates. Using structure-based mutagenesis, we show that catalysis is synchronized in K. setae ECR across the pair of dimers by conformational coupling of catalytic domains and within individual dimers by shared substrate binding sites. Our results provide unprecedented insights into the dynamic organization and synchronized inter- and intra-subunit communications of nature’s most efficient CO2-fixing enzyme during catalysis. ER -