Structure of the peptidoglycan polymerase RodA resolved by evolutionary coupling analysis

Structure of the peptidoglycan polymerase RodA resolved by evolutionary coupling analysis Nature 556, 7699 (2018). doi:10.1038/nature25985 Authors: Megan Sjodt, Kelly Brock, Genevieve Dobihal, Patricia D. A. Rohs, Anna G. Green, Thomas A. Hopf, Alexander J. Meeske, Veerasak Srisuknimit, Daniel Kahne, Suzanne Walker, Debora S. Marks, Thomas G. Bernhardt, David Z. Rudner & Andrew C. Kruse The shape, elongation, division and sporulation (SEDS) proteins are a large family of ubiquitous and essential transmembrane enzymes with critical roles in bacterial cell wall biology. The exact function of SEDS proteins was for a long time poorly understood, but recent work has revealed that the prototypical SEDS family member RodA is a peptidoglycan polymerase—a role previously attributed exclusively to members of the penicillin-binding protein family. This discovery has made RodA and other SEDS proteins promising targets for the development of next-generation antibiotics. However, little is known regarding the molecular basis of SEDS activity, and no structural data are available for RodA or any homologue thereof. Here we report the crystal structure of Thermus thermophilus RodA at a resolution of 2.9 Å, determined using evolutionary covariance-based fold prediction to enable molecular replacement. The structure reveals a ten-pass transmembrane fold with large extracellular loops, one of which is partially disordered. The protein contains a highly conserv...
Source: Nature - Category: Research Authors: Tags: Letter Source Type: research