4EVZ

Structure of HisF-LUCA

Summary for 4EVZ

• Entry DOI: 10.2210/pdb4evz/pdb
• Descriptor: HisF-LUCA, HYDROGENPHOSPHATE ION (3 entities in total)
• Functional Keywords: imidazole glycerol phosphate synthase-luca, lyase
• Biological source: artificial gene
• Total number of polymer chains: 2
• Total formula weight: 56222.80

Authors

Reisinger, B.,Sperl, J.,Rajendran, C.,Merkl, R.,Sterner, R. (deposition date: 2012-04-26, release date: 2013-11-06, Last modification date: 2023-09-13)

Primary citation

Reisinger, B.,Sperl, J.,Holinski, A.,Schmid, V.,Rajendran, C.,Carstensen, L.,Schlee, S.,Blanquart, S.,Merkl, R.,Sterner, R.
Evidence for the existence of elaborate enzyme complexes in the Paleoarchean era.
J.Am.Chem.Soc., 136:122-129, 2014

PubMed 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.

PubMed: 24364418
DOI: 10.1021/ja4115677

Experimental method

X-RAY DIFFRACTION (1.462 Å)