4XVE

17beta-HSD5 in complex with 3-pentyl-2-[(pyridin-2-ylmethyl)sulfanyl]-7-(pyrrolidin-1-ylcarbonyl)quinazolin-4(3H)-one


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.55 Å
  • R-Value Free: 0.203 
  • R-Value Work: 0.179 
  • R-Value Observed: 0.180 

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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Structures of complexes of type 5 17 beta-hydroxysteroid dehydrogenase with structurally diverse inhibitors: insights into the conformational changes upon inhibitor binding.

Amano, Y.Yamaguchi, T.Niimi, T.Sakashita, H.

(2015) Acta Crystallogr D Biol Crystallogr 71: 918-927

  • DOI: https://doi.org/10.1107/S1399004715002175
  • Primary Citation of Related Structures:  
    4WDT, 4WDU, 4WDW, 4WDX, 4XVD, 4XVE

  • PubMed Abstract: 

    Type 5 17β-hydroxysteroid dehydrogenase (17β-HSD5) is an aldo-keto reductase expressed in the human prostate which catalyzes the conversion of androstenedione to testosterone. Testosterone is converted to 5α-dihydrotestosterone, which is present at high concentrations in patients with castration-resistant prostate cancer (CRPC). Inhibition of 17β-HSD5 is therefore considered to be a promising therapy for treating CRPC. In the present study, crystal structures of complexes of 17β-HSD5 with structurally diverse inhibitors derived from high-throughput screening were determined. In the structures of the complexes, various functional groups, including amide, nitro, pyrazole and hydroxyl groups, form hydrogen bonds to the catalytic residues His117 and Tyr55. In addition, major conformational changes of 17β-HSD5 were observed following the binding of the structurally diverse inhibitors. These results demonstrate interactions between 17β-HSD5 and inhibitors at the atomic level and enable structure-based drug design for anti-CRPC therapy.


  • Organizational Affiliation

    Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Aldo-keto reductase family 1 member C3331Homo sapiensMutation(s): 0 
Gene Names: AKR1C3
EC: 1.1.1.64
UniProt & NIH Common Fund Data Resources
Find proteins for P42330 (Homo sapiens)
Explore P42330 
Go to UniProtKB:  P42330
PHAROS:  P42330
GTEx:  ENSG00000196139 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP42330
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
NAP
Query on NAP

Download Ideal Coordinates CCD File 
B [auth A]NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE
C21 H28 N7 O17 P3
XJLXINKUBYWONI-NNYOXOHSSA-N
WDS
Query on WDS

Download Ideal Coordinates CCD File 
C [auth A]3-pentyl-2-[(pyridin-2-ylmethyl)sulfanyl]-7-(pyrrolidin-1-ylcarbonyl)quinazolin-4(3H)-one
C24 H28 N4 O2 S
DSTQURGOCGYFAN-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
WDS Binding MOAD:  4XVE IC50: 2900 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.55 Å
  • R-Value Free: 0.203 
  • R-Value Work: 0.179 
  • R-Value Observed: 0.180 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 55.269α = 90
b = 62.554β = 90
c = 95.655γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
HKL-2000data reduction
HKL-2000data scaling
AMoREphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2015-04-15
    Type: Initial release
  • Version 1.1: 2015-06-10
    Changes: Database references
  • Version 1.2: 2020-02-05
    Changes: Data collection, Derived calculations, Source and taxonomy
  • Version 1.3: 2023-11-08
    Changes: Data collection, Database references, Refinement description