title: Evidence for the existence of elaborate enzyme complexes in the Paleoarchean era.
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)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.
authors.affiliation: Institute of Biophysics and Physical Biochemistry, University of Regensburg , Universitätsstraße 31, D-93053 Regensburg, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Reisinger
authors.forename: Josef
authors.initials: J
authors.lastname: Sperl
authors.forename: Alexandra
authors.initials: A
authors.lastname: Holinski
authors.forename: Veronika
authors.initials: V
authors.lastname: Schmid
authors.forename: Chitra
authors.initials: C
authors.lastname: Rajendran
authors.forename: Linn
authors.initials: L
authors.lastname: Carstensen
authors.forename: Sandra
authors.initials: S
authors.lastname: Schlee
authors.forename: Samuel
authors.initials: S
authors.lastname: Blanquart
authors.forename: Rainer
authors.initials: R
authors.lastname: Merkl
authors.forename: Reinhard
authors.initials: R
authors.lastname: Sterner
mesh_terms: D000619:Aminohydrolases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001105:Archaea / Q000201:enzymology / Q000235:genetics; D018360:Crystallography, X-Ray; D019143:Evolution, Molecular; D053476:Extinction, Biological; D008958:Models, Molecular; D009097:Multienzyme Complexes / Q000737:chemistry* / Q000378:metabolism*; D017510:Protein Folding; D017433:Protein Structure, Secondary
chemical_list: D009097:Multienzyme Complexes; C087227:imidazole glycerol phosphate synthase; D000619:Aminohydrolases