Crystal structure of mevalonate 3,5-bisphosphate decarboxylase reveals insight into the evolution of decarboxylases in the mevalonate metabolic pathways

被引：6

作者：

Aoki, Mizuki ^{[1
]}

Vinokur, Jeffrey ^{[2
]}

Motoyama, Kento ^{[1
]}

Ishikawa, Rino ^{[1
]}

Collazo, Michael ^{[3
]}

Cascio, Duilio ^{[3
]}

Sawaya, Michael R. ^{[4
]}

Ito, Tomokazu ^{[1
]}

Bowie, James U. ^{[2
]}

Hemmi, Hisashi ^{[1
]}

机构：

[1] Nagoya Univ, Grad Sch Bioagr Sci, Dept Appl Biosci, Furo Cho, Nagoya, Aichi, Japan

[2] Univ Calif Los Angeles UCLA, UCLA DOE Inst Mol Biol Inst, Dept Chem & Biochem, Los Angeles, CA USA

[3] Univ Calif Los Angeles UCLA, UCLA DOE Inst Genom & Prote, Dept Biol Chem, Los Angeles, CA USA

[4] Univ Calif Los Angeles UCLA, UCLA DOE Inst Genom & Prote, Howard Hughes Med Inst, Los Angeles, CA USA

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2022年 / 298卷 / 07期

关键词：

DIPHOSPHATE DECARBOXYLASE; KINASE; BINDING; ENZYME; INHIBITION; MUTATION;

D O I：

10.1016/j.jbc.2022.102111

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 phospho-mevalonate 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 be-tween 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 -indepen-dent) 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 physio-logical importance of ligand binding as well as a possible novel regulatory system employed by the Thermoplasma-type mevalonate pathway.

引用

页数：12