Open AccessAn Unexpected Oxidosqualene Cyclase Active Site Architecture in the Iris tectorum Multifunctional α-Amyrin Synthase
Author(s) -
Shidan Wu,
Fan Zhang,
Wenbo Xiong,
István Molnár,
Jincai Liang,
Aijia Ji,
Li Yu,
Caixia Wang,
Shengliang Wang,
Zhongqiu Liu,
Ruibo Wu,
Lixin Duan
Publication year - 2020
Publication title -
acs catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.898
H-Index - 198
ISSN - 2155-5435
DOI - 10.1021/acscatal.0c03231
Subject(s) - active site , mutagenesis , catalytic triad , chemistry , atp synthase , biology , biochemistry , drug discovery , stereochemistry , computational biology , microbiology and biotechnology , catalysis , enzyme , mutation , gene
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.