3G5M

Synthesis of Casimiroin and Optimization of Its Quinone Reductase 2 and Aromatase Inhibitory activity


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.84 Å
  • R-Value Free: 0.242 
  • R-Value Work: 0.182 
  • R-Value Observed: 0.185 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Synthesis of casimiroin and optimization of its quinone reductase 2 and aromatase inhibitory activities.

Maiti, A.Reddy, P.V.Sturdy, M.Marler, L.Pegan, S.D.Mesecar, A.D.Pezzuto, J.M.Cushman, M.

(2009) J Med Chem 52: 1873-1884

  • DOI: https://doi.org/10.1021/jm801335z
  • Primary Citation of Related Structures:  
    3G5M, 3GAM

  • PubMed Abstract: 

    An efficient method has been developed to synthesize casimiroin (1), a component of the edible fruit of Casimiroa edulis, on a multigram scale in good overall yield. The route was versatile enough to provide an array of compound 1 analogues that were evaluated as QR2 and aromatase inhibitors. In addition, X-ray crystallography studies of QR2 in complex with compound 1 and one of its more potent analogues has provided insight into the mechanism of action of this new series of QR2 inhibitors. The initial biological investigations suggest that compound 1 and its analogues merit further investigation as potential chemopreventive or chemotherapeutic agents.


  • Organizational Affiliation

    Department of Medicinal Chemistry and Molecular Pharmacology, School of Pharmacy and Pharmaceutical Sciences, and the Purdue Cancer Center, Purdue University, West Lafayette, Indiana 47907, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Ribosyldihydronicotinamide dehydrogenase [quinone]
A, B
231Homo sapiensMutation(s): 0 
Gene Names: NQO2NMOR2
EC: 1.10.99.2
UniProt & NIH Common Fund Data Resources
Find proteins for P16083 (Homo sapiens)
Explore P16083 
Go to UniProtKB:  P16083
PHAROS:  P16083
GTEx:  ENSG00000124588 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP16083
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
FAD
Query on FAD

Download Ideal Coordinates CCD File 
G [auth A],
J [auth B]
FLAVIN-ADENINE DINUCLEOTIDE
C27 H33 N9 O15 P2
VWWQXMAJTJZDQX-UYBVJOGSSA-N
XM5
Query on XM5

Download Ideal Coordinates CCD File 
D [auth A],
E [auth A],
F [auth A],
I [auth B]
6-methoxy-9-methyl[1,3]dioxolo[4,5-h]quinolin-8(9H)-one
C12 H11 N O4
DPXXJCMMMXZVSW-UHFFFAOYSA-N
ZN
Query on ZN

Download Ideal Coordinates CCD File 
C [auth A],
H [auth B]
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
XM5 Binding MOAD:  3G5M IC50: 5.41e+4 (nM) from 1 assay(s)
BindingDB:  3G5M IC50: 5.41e+4 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.84 Å
  • R-Value Free: 0.242 
  • R-Value Work: 0.182 
  • R-Value Observed: 0.185 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 56.734α = 90
b = 84.231β = 90
c = 106.312γ = 90
Software Package:
Software NamePurpose
SERGUIdata collection
CCP4model building
REFMACrefinement
HKL-2000data reduction
HKL-2000data scaling
CCP4phasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2009-03-24
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2023-09-06
    Changes: Data collection, Database references, Derived calculations, Refinement description