An alternative mechanism of product chain-length determination in type III geranylgeranyl diphosphate synthase

Hisashi Hemmi, Motoyoshi Noike, Toru Nakayama, Tokuzo Nishino

Research output: Contribution to journalArticlepeer-review

46 Citations (Scopus)

Abstract

(All-E) prenyl diphosphate synthases catalyze the consecutive condensation of isopentenyl diphosphates with allylic prenyl diphosphates, producing products with various chain-lengths that are unique for each enzyme. Some short-chain (all-E) prenyl diphosphate synthases, i.e. farnesyl diphosphate synthases and geranylgeranyl diphosphate synthases contain characteristic amino acid sequences around the allylic substrate binding sites, which have been shown to play a role in determining the chain-length of the product. However, among these enzymes, which are classified into several types based on the possessive patterns of such characteristics, type III geranylgeranyl diphosphate synthases, which consist of enzymes from eukaryotes (excepting plants), lack these features. In this study, we report that mutagenesis at the second position before the conserved G(Q/E) motif, which is distant from the well-studied region, affects the chain-length of the product for a type III geranylgeranyl diphosphate synthase from Saccharomyces cerevisiae. This clearly suggests that a novel mechanism is operative in the product determination for this type of enzyme. We also show herein that mutagenesis at the corresponding position of an archaeal medium-chain enzyme also alters its product specificity. These results provide valuable information on the molecular evolution of (all-E) prenyl diphosphate synthases.

Original languageEnglish
Pages (from-to)2186-2194
Number of pages9
JournalEuropean Journal of Biochemistry
Volume270
Issue number10
DOIs
Publication statusPublished - 2003 May 1

Keywords

  • Geranylgeranyl diphosphate synthase
  • Hexaprenyl diphosphate synthase
  • Molecular evolution
  • Mutagenesis
  • Prenyltransferase

ASJC Scopus subject areas

  • Biochemistry

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