3CZR

Crystal Structure of Human 11-beta-Hydroxysteroid Dehydrogenase (HSD1) in Complex with Arylsulfonylpiperazine Inhibitor

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.35 Å
  • R-Value Free: 0.247 
  • R-Value Work: 0.219 
  • R-Value Observed: 0.221 

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This is version 1.3 of the entry. See complete history. 


Literature

Discovery and Initial SAR of Arylsulfonylpiperazine Inhibitors of 11beta-Hydroxysteroid Dehydrogenase Type 1 (11beta-HSD1)

Sun, D., Wang, Z., Di, Y., Jaen, J.C., Labelle, M., Ma, J., Miao, S., Sudom, A., Tang, L., Tomooka, C.S., Tu, H., Ursu, S., Walker, N., Yan, X., Ye, Q., Powers, J.P.

(2008) Bioorg Med Chem Lett 18: 3513-3516

  • DOI: https://doi.org/10.1016/j.bmcl.2008.05.025
  • Primary Citation of Related Structures:  
    3CZR

  • PubMed Abstract: 

    High-throughput screening of a small-molecule compound library resulted in the identification of a series of arylsulfonylpiperazines that are potent and selective inhibitors of human 11beta-Hydroxysteroid Dehydrogenase Type 1 (11beta-HSD1). Optimization of the initial lead resulted in the discovery of compound (R)-45 (11beta-HSD1 IC(50)=3nM).

    • Organizational Affiliation: 

    Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, USA. [email protected]


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Corticosteroid 11-beta-dehydrogenase isozyme 1
A, B
286Homo sapiensMutation(s): 1 
Gene Names: HSD11B1, HSD11, HSD11L
EC: 1.1.1.146 (PDB Primary Data), 1.1.1.201 (UniProt)
UniProt & NIH Common Fund Data Resources
Find proteins for P28845 (Homo sapiens)
Explore P28845 
Go to UniProtKB:  P28845
PHAROS:  P28845
GTEx:  ENSG00000117594 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP28845
Sequence Annotations
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  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
3CZ BindingDB:  3CZR IC50: min: 3, max: 57 (nM) from 3 assay(s)
EC50: 57 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.35 Å
  • R-Value Free: 0.247 
  • R-Value Work: 0.219 
  • R-Value Observed: 0.221 
  • Space Group: P 31 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 110.216α = 90
b = 110.216β = 90
c = 132.991γ = 120
Software Package:
Software NamePurpose
REFMACrefinement
ADSCdata collection
MOSFLMdata reduction
SCALAdata scaling

Structure Validation

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Ligand Structure Quality Assessment 


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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2008-06-17
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2021-10-20
    Changes: Database references, Derived calculations, Source and taxonomy
  • Version 1.3: 2024-02-21
    Changes: Data collection