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

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.

SUBMITTER: Wu S

PROVIDER: S-EPMC8297885 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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

Wu Shidan S Zhang Fan F Xiong Wenbo W Molnár István I Liang Jincai J Ji Aijia A Wang Caixia C Wang Shengliang S Liu Zhongqiu Z Wu Ruibo R Duan Lixin L

ACS catalysis 20200804 16

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 co ...[more]

PMID: 34306805

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