Complex structures of MoeN5 with substrate analogues suggest sequential catalytic mechanism

Lilan Zhang, Tzu Ping Ko, Satish R. Malwal, Weidong Liu, Shuyu Zhou, Xuejing Yu, Eric Oldfield, Rey Ting Guo, Chun Chi Chen

Research output: Contribution to journalArticlepeer-review


The antibiotic moenomycin A is a phosphoglycerate derivative with a C 25 -moenocinyl chain and a branched oligosaccharide. Formation of the C 25 -chain is catalyzed by the enzyme MoeN5 with geranyl pyrophosphate (GPP) and the sugar-linked 2-Z,E-farnesyl-3-phosphoglycerate (FPG) as its substrates. Previous complex crystal structures with GPP and long-chain alkyl glycosides suggested that GPP binds to the S1 site in a similar way as in most other α-helical prenyltransferases (PTs), and FPG is likely to assume a bent conformation in the S2 site. However, two FPG derivatives synthesized in the current study were found in the S1 site rather than S2 in their complex crystal structures with MoeN5. Apparently S1 is the preferred site for prenyl-containing ligand, and S2 binding may proceed only after S1 is occupied. Thus, like most trans-type PTs, MoeN5 may employ a sequential ionization-condensation-elimination mechanism that involves a carbocation intermediate.

Original languageEnglish (US)
Pages (from-to)800-805
Number of pages6
JournalBiochemical and Biophysical Research Communications
Issue number4
StatePublished - Apr 16 2019


  • Antibiotics biosynthesis
  • Prenyltransferase
  • Sso7d protein tag
  • X-ray crystallography
  • moenomycin

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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