Studies on geranylgeranyl diphosphate synthase from rat liver: Specific inhibition by 3-azageranylgeranyl diphosphate

Hiroshi Sagami, Tatsumi Korenaga, Kyozo Ogura, Arthur Steiger, Hyung Jung Pyun, Robert M. Coates

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)

Abstract

Geranylgeranyl diphosphate synthase from rat liver was separated from farnesyl diphosphate synthase, the most abundant and widely occurring prenyltransferase, by DEAE-Toyopearl column chromatography. The enzyme catalyzed the formation of E,E,E-geranylgeranyl diphosphate (V) from isopentenyl diphosphate (II) and dimethylallyl diphosphate (I), geranyl diphosphate (III), or farnesyl diphosphate (IV) with relative velocities of 0.09:0.15:1. 3-Azageranylgeranyl diphosphate (VII), designed as a transition-state analog for the geranylgeranyl diphosphate synthase reaction, was synthesized and found to act as a specific inhibitor for this synthase, but not for farnesyl diphosphate synthase. Diphosphate V and its Z,E,E-isomer (VI) also inhibited geranylgeranyl diphosphate synthase, but the effect was not as striking as that of the aza analog VII. Specific inhibition of geranylgeranyl diphosphate synthase by VII was also observed in experiments with 100,000g supernatants of rat brain and liver homogenates which contained isopentenyl diphosphate isomerase and prenyltransferases including farnesyl diphosphate synthase as well as geranylgeranyl diphosphate synthase. For farnesyl:protein transferase from rat brain, however, the aza compound did not show a stronger inhibitory effect than E,E,E-geranylgeranyl diphosphate.

Original languageEnglish
Pages (from-to)314-320
Number of pages7
JournalArchives of Biochemistry and Biophysics
Volume297
Issue number2
DOIs
Publication statusPublished - 1992 Sep

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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