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 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


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. daqings@amgen.com


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
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
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
NAP
Query on NAP
Download Ideal Coordinates CCD File 
C [auth A],
E [auth B]		NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE
C21 H28 N7 O17 P3
XJLXINKUBYWONI-NNYOXOHSSA-N
CPS
Query on CPS
Download Ideal Coordinates CCD File 
F [auth B]3-[(3-CHOLAMIDOPROPYL)DIMETHYLAMMONIO]-1-PROPANESULFONATE
C32 H58 N2 O7 S
UMCMPZBLKLEWAF-BCTGSCMUSA-N
3CZ
Query on 3CZ
Download Ideal Coordinates CCD File 
D [auth A](2R)-1-[(4-tert-butylphenyl)sulfonyl]-2-methyl-4-(4-nitrophenyl)piperazine
C21 H27 N3 O4 S
SOFGQQQVQZQJFS-MRXNPFEDSA-N
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)
Binding MOAD:  3CZR IC50: 3 (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

View Full Validation Report



Ligand Structure Quality Assessment 


View more in-depth experimental data
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