class I sesquiterpene synthase

Experimental Data Snapshot

  • Resolution: 1.47 Å
  • R-Value Free: 0.198 
  • R-Value Work: 0.171 
  • R-Value Observed: 0.172 

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Structural Insights into Three Sesquiterpene Synthases for the Biosynthesis of Tricyclic Sesquiterpenes and Chemical Space Expansion by Structure-Based Mutagenesis.

Lou, T.Li, A.Xu, H.Pan, J.Xing, B.Wu, R.Dickschat, J.S.Yang, D.Ma, M.

(2023) J Am Chem Soc 

  • DOI: https://doi.org/10.1021/jacs.3c00278
  • Primary Citation of Related Structures:  
    8H4P, 8H6Q, 8H6U, 8H72

  • PubMed Abstract: 

    The cyclization of farnesyl diphosphate (FPP) into highly strained polycyclic sesquiterpenes is challenging. We here determined the crystal structures of three sesquiterpene synthases (STSs, namely, BcBOT2, DbPROS, and CLM1) catalyzing the biosynthesis of the tricyclic sesquiterpenes presilphiperfolan-8β-ol ( 1 ), Δ 6 -protoilludene ( 2 ), and longiborneol ( 3 ). All three STS structures contain a substrate mimic, the benzyltriethylammonium cation (BTAC), in their active sites, providing ideal templates for quantum mechanics/molecular mechanics (QM/MM) analyses toward their catalytic mechanisms. The QM/MM-based molecular dynamics (MD) simulations revealed the cascade reactions toward the enzyme products, and different key active site residues that play important roles in stabilizing reactive carbocation intermediates along the three pathways. Site-directed mutagenesis experiments confirmed the roles of these key residues and concomitantly resulted in 17 shunt products ( 4 - 20 ). Isotopic labeling experiments addressed the key hydride and methyl migrations toward the main and several shunt products. These combined methods provided deep insights into the catalytic mechanisms of the three STSs and demonstrated how the chemical space of STSs can rationally be expanded, which may facilitate applications in synthetic biology approaches toward pharmaceutical and perfumery agents.

  • Organizational Affiliation

    State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Haidian District, Beijing 100191, China.

Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Longiborneol synthase CLM1
A, B
344Fusarium graminearum PH-1Mutation(s): 0 
Gene Names: CLM1FG10397FGRAMPH1_01T07999
EC: 4.2.3
Find proteins for I1S104 (Gibberella zeae (strain ATCC MYA-4620 / CBS 123657 / FGSC 9075 / NRRL 31084 / PH-1))
Explore I1S104 
Go to UniProtKB:  I1S104
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupI1S104
Sequence Annotations
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
BTM (Subject of Investigation/LOI)
Query on BTM

Download Ideal Coordinates CCD File 
D [auth A],
I [auth B]
C13 H22 N
PPV (Subject of Investigation/LOI)
Query on PPV

Download Ideal Coordinates CCD File 
C [auth A],
H [auth B]
H4 O7 P2
MG (Subject of Investigation/LOI)
Query on MG

Download Ideal Coordinates CCD File 
E [auth A]
F [auth A]
G [auth A]
J [auth B]
K [auth B]
E [auth A],
F [auth A],
G [auth A],
J [auth B],
K [auth B],
L [auth B]
Experimental Data & Validation

Experimental Data

  • Resolution: 1.47 Å
  • R-Value Free: 0.198 
  • R-Value Work: 0.171 
  • R-Value Observed: 0.172 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 76.704α = 90
b = 59.416β = 98.33
c = 83.548γ = 90
Software Package:
Software NamePurpose
PDB_EXTRACTdata extraction
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

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Ligand Structure Quality Assessment 

Entry History & Funding Information

Deposition Data

Funding OrganizationLocationGrant Number
National Natural Science Foundation of China (NSFC)China22077007, 21877002

Revision History  (Full details and data files)

  • Version 1.0: 2023-08-23
    Type: Initial release