7T71

Crystal Structure of Mevalonate 3,5-Bisphosphate Decarboxylase from Picrophilus Torridus

Summary for 7T71

• Entry DOI: 10.2210/pdb7t71/pdb
• Descriptor: Mevalonate 3,5-bisphosphate decarboxylase, OLEIC ACID (3 entities in total)
• Functional Keywords: mevalonate pathway, mevalonic acid, lyase
• Biological source: Picrophilus torridus DSM 9790
• Total number of polymer chains: 2
• Total formula weight: 84772.03

Authors

Vinokur, J.M.,Sawaya, M.R.,Cascio, D.,Collazo, M.,Bowie, J.U. (deposition date: 2021-12-14, release date: 2021-12-22, Last modification date: 2023-10-25)

Primary citation

Aoki, M.,Vinokur, J.,Motoyama, K.,Ishikawa, R.,Collazo, M.,Cascio, D.,Sawaya, M.R.,Ito, T.,Bowie, J.U.,Hemmi, H.
Crystal structure of mevalonate 3,5-bisphosphate decarboxylase reveals insight into the evolution of decarboxylases in the mevalonate metabolic pathways.
J.Biol.Chem., 298:102111-102111, 2022

PubMed Abstract: Mevalonate 3,5-bisphosphate decarboxylase is involved in the recently discovered Thermoplasma-type mevalonate pathway. The enzyme catalyzes the elimination of the 3-phosphate group from mevalonate 3,5-bisphosphate as well as concomitant decarboxylation of the substrate. This entire reaction of the enzyme resembles the latter half-reactions of its homologs, diphosphomevalonate decarboxylase and phosphomevalonate decarboxylase, which also catalyze ATP-dependent phosphorylation of the 3-hydroxyl group of their substrates. However, the crystal structure of mevalonate 3,5-bisphosphate decarboxylase and the structural reasons of the difference between reactions catalyzed by the enzyme and its homologs are unknown. In this study, we determined the X-ray crystal structure of mevalonate 3,5-bisphosphate decarboxylase from Picrophilus torridus, a thermoacidophilic archaeon of the order Thermoplasmatales. Structural and mutational analysis demonstrated the importance of a conserved aspartate residue for enzyme activity. In addition, although crystallization was performed in the absence of substrate or ligands, residual electron density having the shape of a fatty acid was observed at a position overlapping the ATP-binding site of the homologous enzyme, diphosphomevalonate decarboxylase. This finding is in agreement with the expected evolutionary route from phosphomevalonate decarboxylase (ATP-dependent) to mevalonate 3,5-bisphosphate decarboxylase (ATP-independent) through the loss of kinase activity. We found that the binding of geranylgeranyl diphosphate, an intermediate of the archeal isoprenoid biosynthesis pathway, evoked significant activation of mevalonate 3,5-bisphosphate decarboxylase, and several mutations at the putative geranylgeranyl diphosphate-binding site impaired this activation, suggesting the physiological importance of ligand binding as well as a possible novel regulatory system employed by the Thermoplasma-type mevalonate pathway.

PubMed: 35690147
DOI: 10.1016/j.jbc.2022.102111

Experimental method

X-RAY DIFFRACTION (2.19 Å)