Evidence for the Existence of Elaborate Enzyme Complexes in the Paleoarchean Era

Bernd Reisinger (1) , Josef Sperl (1) , Alexandra Holinski (1) , Veronika Schmid (1) , Chitra Rajendran (1) , Linn Carstensen (1) , Sandra Schlee (1) , Samuel Blanquart (2) , Rainer Merkl (1) , Reinhard Sterner (1)

1 Institut für Biophysik und physikalische Biochemie
2 BONSAI - Bioinformatics and Sequence Analysis

: Due to the lack of macromolecular fossils, the enzymatic repertoire of extinct species has remained largely unknown to date. In an attempt to solve this problem, we have characterized a cyclase subunit (HisF) of the imidazole glycerol phosphate synthase (ImGP-S), which was reconstructed from the era of the last universal common ancestor of cellular organisms (LUCA). As observed for contemporary HisF proteins, the crystal structure of LUCA-HisF adopts the (βα)8-barrel architecture, one of the most ancient folds. Moreover, LUCA-HisF (i) resembles extant HisF proteins with regard to internal 2-fold symmetry, active site residues, and a stabilizing salt bridge cluster, (ii) is thermostable and shows a folding mechanism similar to that of contemporary (βα)8-barrel enzymes, (iii) displays high catalytic activity, and (iv) forms a stable and functional complex with the glutaminase subunit (HisH) of an extant ImGP-S. Furthermore, we show that LUCA-HisF binds to a reconstructed LUCA-HisH protein with high affinity. Our findings suggest that the evolution of highly efficient enzymes and enzyme complexes has already been completed in the LUCA era, which means that sophisticated catalytic concepts such as substrate channeling and allosteric communication existed already 3.5 billion years ago.

Domaines: Bio-Informatique, Biologie Systémique [q-bio.QM]; Bio-informatique [q-bio.QM]

Bernd Reisinger, Josef Sperl, Alexandra Holinski, Veronika Schmid, Chitra Rajendran, et al.. Evidence for the Existence of Elaborate Enzyme Complexes in the Paleoarchean Era. Journal of the American Chemical Society, 2014, pp.122-9. ⟨10.1021/ja4115677⟩. ⟨hal-00924047⟩