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; Ruibo Wu; Lixin Duan

doi:10.1021/acscatal.0c03231

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
, Ruibo Wu
, Lixin Duan

Research output: Contribution to journal › Article › peer-review

33 Scopus citations

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 active site architecture in ItOSC2 underscores the plasticity of terpene cyclase catalytic mechanisms and opens avenues for protein engineering toward custom designed OSCs.

Original language	English (US)
Pages (from-to)	9515-9520
Number of pages	6
Journal	ACS Catalysis
Volume	10
Issue number	16
DOIs	https://doi.org/10.1021/acscatal.0c03231
State	Published - Aug 21 2020

Keywords

QM/MM
enzyme catalysis
enzyme promiscuity
oxidosqualene cyclase
triterpene

ASJC Scopus subject areas

Catalysis
General Chemistry

Access to Document

10.1021/acscatal.0c03231

Cite this

@article{727ffcd3f6b04af7af530905b2052e18,

title = "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 active site architecture in ItOSC2 underscores the plasticity of terpene cyclase catalytic mechanisms and opens avenues for protein engineering toward custom designed OSCs.",

keywords = "QM/MM, enzyme catalysis, enzyme promiscuity, oxidosqualene cyclase, triterpene",

author = "Shidan Wu and Fan Zhang and Wenbo Xiong and Istv{\'a}n Moln{\'a}r and Jincai Liang and Aijia Ji and Yu Li and Caixia Wang and Shengliang Wang and Zhongqiu Liu and Ruibo Wu and Lixin Duan",

note = "Publisher Copyright: {\textcopyright} 2020 American Chemical Society.",

year = "2020",

month = aug,

day = "21",

doi = "10.1021/acscatal.0c03231",

language = "English (US)",

volume = "10",

pages = "9515--9520",

journal = "ACS Catalysis",

issn = "2155-5435",

publisher = "American Chemical Society",

number = "16",

}

TY - JOUR

T1 - An Unexpected Oxidosqualene Cyclase Active Site Architecture in the Iris tectorum Multifunctional α-Amyrin Synthase

AU - Wu, Shidan

AU - Zhang, Fan

AU - Xiong, Wenbo

AU - Molnár, István

AU - Liang, Jincai

AU - Ji, Aijia

AU - Li, Yu

AU - Wang, Caixia

AU - Wang, Shengliang

AU - Liu, Zhongqiu

AU - Wu, Ruibo

AU - Duan, Lixin

PY - 2020/8/21

Y1 - 2020/8/21

N2 - 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 active site architecture in ItOSC2 underscores the plasticity of terpene cyclase catalytic mechanisms and opens avenues for protein engineering toward custom designed OSCs.

AB - 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 active site architecture in ItOSC2 underscores the plasticity of terpene cyclase catalytic mechanisms and opens avenues for protein engineering toward custom designed OSCs.

KW - QM/MM

KW - enzyme catalysis

KW - enzyme promiscuity

KW - oxidosqualene cyclase

KW - triterpene

UR - https://www.scopus.com/pages/publications/85091397122

UR - https://www.scopus.com/pages/publications/85091397122#tab=citedBy

U2 - 10.1021/acscatal.0c03231

DO - 10.1021/acscatal.0c03231

M3 - Article

AN - SCOPUS:85091397122

SN - 2155-5435

VL - 10

SP - 9515

EP - 9520

JO - ACS Catalysis

JF - ACS Catalysis

IS - 16

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this