New role of flavin as a general acid-base catalyst with no redox function in type 2 isopentenyl-diphosphate isomerase

Hideaki Unno, Satoshi Yamashita, Yosuke Ikeda, Shin Ya Sekiguchi, Norie Yoshida, Tohru Yoshimura, Masami Kusunoki, Toru Nakayama, Tokuzo Nishino, Hisashi Hemmi

研究成果: Article査読

41 被引用数 (Scopus)

抄録

Using FMN and a reducing agent such as NAD(P)H, type 2 isopentenyl-diphosphate isomerase catalyzes isomerization between isopentenyl diphosphate and dimethylallyl diphosphate, both of which are elemental units for the biosynthesis of highly diverse isoprenoid compounds. Although the flavin cofactor is expected to be integrally involved in catalysis, its exact role remains controversial. Here we report the crystal structures of the substrate-free and complex forms of type 2 isopentenyl-diphosphate isomerase from the thermoacidophilic archaeon Sulfolobus shibatae, not only in the oxidized state but also in the reduced state. Based on the active-site structures of the reduced FMN-substrate-enzyme ternary complexes, which are in the active state, and on the data from site-directed mutagenesis at highly conserved charged or polar amino acid residues around the active site, we demonstrate that only reduced FMN, not amino acid residues, can catalyze proton addition/elimination required for the isomerase reaction. This discovery is the first evidence for this long suspected, but previously unobserved, role of flavins just as a general acid-base catalyst without playing any redox roles, and thereby expands the known functions of these versatile coenzymes.

本文言語English
ページ(範囲)9160-9167
ページ数8
ジャーナルJournal of Biological Chemistry
284
14
DOI
出版ステータスPublished - 2009 4月 3

ASJC Scopus subject areas

  • 生化学
  • 分子生物学
  • 細胞生物学

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