Product chain-length determination mechanism of Z,E-farnesyl diphosphate synthase

Motoyoshi Noike, Takanori Ambo, Sayaka Kikuchi, Toshihide Suzuki, Satoshi Yamashita, Seiji Takahashi, Hirofumi Kurokawa, Sebabrata Mahapatra, Dean C. Crick, Tanetoshi Koyama

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

cis-Prenyltransferases catalyze the consecutive condensation of isopentenyl diphosphate (IPP) with allylic prenyl diphosphates, producing Z,E-mixed prenyl diphosphate. The Mycobacterium tuberculosis Z,E-farnesyl diphosphate synthase Rv1086 catalyzes the condensation of one molecule of IPP with geranyl diphosphate to yield Z,E-farnesyl diphosphate and is classified as a short-chain cis-prenyltransferase. To elucidate the chain-length determination mechanism of the short-chain cis-prenyltransferase, we introduced some substitutive mutations at the characteristic amino acid residues of Rv1086. Among the mutants constructed, L84A showed a dramatic change of catalytic function to synthesize longer prenyl chain products than that of wild type, indicating that Leu84 of Rv1086 plays an important role in product chain-length determination. Mutagenesis at the corresponding residue of a medium-chain cis-prenyltransferase, Micrococcus luteus B-P 26 undecaprenyl diphosphate synthase also resulted in the production of different prenyl chain length from the intrinsic product, suggesting that this position also plays an important role in product chain-length determination for medium-chain cis-prenyltransferases.

Original languageEnglish
Pages (from-to)17-22
Number of pages6
JournalBiochemical and biophysical research communications
Volume377
Issue number1
DOIs
Publication statusPublished - 2008 Dec 5

Keywords

  • Chain-length determination mechanism
  • Isoprenoid
  • Mutagenesis
  • Mycobacterium tuberculosis
  • Prenyl diphosphate synthase
  • Prenyltransferase
  • Undecaprenyl diphosphate synthase

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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