7Y3V

Crystal structure of CdpNPT in complex with harmane


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.43 Å
  • R-Value Free: 0.236 
  • R-Value Work: 0.217 
  • R-Value Observed: 0.237 

Starting Model: experimental
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Ligand Structure Quality Assessment 

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Literature

Catalytic potential of a fungal indole prenyltransferase toward beta-carbolines, harmine and harman, and their prenylation effects on antibacterial activity.

Hamdy, S.A.Kodama, T.Nakashima, Y.Han, X.Morita, H.

(2022) J Biosci Bioeng 134: 311-317

  • DOI: https://doi.org/10.1016/j.jbiosc.2022.07.004
  • Primary Citation of Related Structures:  
    7Y3V

  • PubMed Abstract: 

    The prenylation of compounds has attracted much attention, since it often adds bioactivity to non-prenylated compounds. We employed an enzyme assay with CdpNPT, an indole prenyltransferase from Aspergillus fumigatus with two naturally occurring β-carbolines, harmine (3) and harman (4) as prenyl acceptors, in the presence of dimethylallyl diphosphate (DMAPP) as the prenyl donor. The enzyme accepted these two prenyl acceptor substrates to produce 6-(3',3'-dimethylallyl)harmine (5) from 3 and 9-(3',3'-dimethylallyl)harman (6) and 6-(3',3'-dimethylallyl)harman (7) from 4. The X-ray crystal structure analysis of the CdpNPT (38-440) truncated mutant complexed with 4, and docking simulation studies of DMAPP to the crystal structure of the CdpNPT (38-440) mutant, suggested that CdpNPT could employ the two-step prenylation mechanism to produce 7, while the enzyme produced 6 with either one- or two-step prenylation mechanisms. Furthermore, the antibacterial assays revealed that the 3',3'-dimethylallylation of 3 and 4, as well as harmol (1), at C-6 enhanced the activities against Staphylococcus aureus and Bacillus subtilis.


  • Organizational Affiliation

    Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Kasr El-Aini St., Cairo 11562, Egypt; Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Cyclic dipeptide N-prenyltransferase
A, B, C, D
404Aspergillus fumigatusMutation(s): 0 
Gene Names: cdpNPT
EC: 3.4.11.17 (UniProt), 2.5.1 (UniProt)
UniProt
Find proteins for D1D8L6 (Aspergillus fumigatus)
Explore D1D8L6 
Go to UniProtKB:  D1D8L6
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupD1D8L6
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
CN9 (Subject of Investigation/LOI)
Query on CN9

Download Ideal Coordinates CCD File 
G [auth A]1-methyl-9H-pyrido[3,4-b]indole
C12 H10 N2
PSFDQSOCUJVVGF-UHFFFAOYSA-N
PO4
Query on PO4

Download Ideal Coordinates CCD File 
E [auth A]
F [auth A]
H [auth B]
I [auth B]
J [auth C]
PHOSPHATE ION
O4 P
NBIIXXVUZAFLBC-UHFFFAOYSA-K
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.43 Å
  • R-Value Free: 0.236 
  • R-Value Work: 0.217 
  • R-Value Observed: 0.237 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 84.655α = 90
b = 157.237β = 90
c = 161.897γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
Aimlessdata scaling
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 

Created with Raphaël 2.3.0Worse 01 BetterLigand structure goodness of fit to experimental dataBest fitted CN9Click on this verticalbar to view details

Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Japan Society for the Promotion of Science (JSPS)Japan22H02777
Japan Society for the Promotion of Science (JSPS)Japan22K15303

Revision History  (Full details and data files)

  • Version 1.0: 2023-04-05
    Type: Initial release
  • Version 1.1: 2023-11-29
    Changes: Data collection, Refinement description