Evidence
for the Existence of Elaborate Enzyme Complexes
in the Paleoarchean Era
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Abstract
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)<sub>8</sub>-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)<sub>8</sub>-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
