An Unexpected Oxidosqualene Cyclase Active Site Architecture in the Iris tectorum Multifunctional α-Amyrin Synthase

Shidan Wu, Fan Zhang, Wenbo Xiong, István Molnár, Jincai Liang, Aijia Ji, Yu Li, Caixia Wang, Shengliang Wang, Zhongqiu Liu (Corresponding Author), Ruibo Wu (Corresponding Author), Lixin Duan (Corresponding Author)

Research output: Contribution to journalArticleScientificpeer-review

7 Citations (Scopus)

Abstract

Ordered polycyclization catalyzed by oxidosqualene synthases (OSCs) morph a common linear precursor into structurally complex and diverse triterpene scaffolds with varied bioactivities. We identified three OSCs from Iris tectorum. ItOSC2 is a rare multifunctional α-amyrin synthase. Sequence comparisons, site-directed mutagenesis and multiscale simulations revealed that three spatially clustered residues, Y531/L256/L258 form an unusual Y-LL triad at the active site, replacing the highly conserved W-xY triad occurring in other amyrin synthases. The discovery of this unprecedented active site architecture in ItOSC2 underscores the plasticity of terpene cyclase catalytic mechanisms and opens new avenues for protein engineering towards custom designed OSCs.

Original languageEnglish
Pages (from-to)9515-9520
Number of pages6
JournalACS Catalysis
Volume10
Issue number16
DOIs
Publication statusPublished - 21 Aug 2020
MoE publication typeA1 Journal article-refereed

Keywords

  • enzyme catalysis
  • enzyme promiscuity
  • oxidosqualene cyclase
  • QM/MM
  • triterpene

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