1XU7

Crystal Structure of the Interface Open Conformation of Tetrameric 11b-HSD1


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.217 
  • R-Value Work: 0.197 
  • R-Value Observed: 0.198 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Conformational Flexibility in Crystal Structures of Human 11beta-hydroxysteroid dehydrogenase type I provide insights into glucocorticoid interconversion and enzyme regulation.

Hosfield, D.J.Wu, Y.Skene, R.J.Hilger, M.Jennings, A.Snell, G.P.Aertgeerts, K.

(2005) J Biol Chem 280: 4639-4648

  • DOI: https://doi.org/10.1074/jbc.M411104200
  • Primary Citation of Related Structures:  
    1XU7, 1XU9

  • PubMed Abstract: 

    Human 11beta-hydroxysteroid dehydrogenase type I (11beta-HSD1) is an ER-localized membrane protein that catalyzes the interconversion of cortisone and cortisol. In adipose tissue, excessive cortisol production through 11beta-HSD1 activity has been implicated in the pathogenesis of type II diabetes and obesity. We report here biophysical, kinetic, mutagenesis, and structural data on two ternary complexes of 11beta-HSD1. The combined results reveal flexible active site interactions relevant to glucocorticoid recognition and demonstrate how four 11beta-HSD1 C termini converge to form an as yet uncharacterized tetramerization motif. A C-terminal Pro-Cys motif is localized at the center of the tetramer and forms reversible enzyme disulfides that alter enzyme activity. Conformational flexibility at the tetramerization interface is coupled to structural changes at the enzyme active site suggesting how the central Pro-Cys motif may regulate enzyme activity. Together, the crystallographic and biophysical data provide a structural framework for understanding 11beta-HSD1 activities and will ultimately facilitate the development of specific inhibitors.


  • Organizational Affiliation

    Syrrx Inc., San Diego, California 92121, USA. david.hosfield@syrrx.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, C, D
286Homo sapiensMutation(s): 1 
Gene Names: HSD11B1HSD11HSD11L
EC: 1.1.1.146
Membrane Entity: Yes 
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
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.217 
  • R-Value Work: 0.197 
  • R-Value Observed: 0.198 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 56.43α = 90
b = 159.625β = 93.07
c = 73.544γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
HKL-2000data reduction
CCP4data scaling
SHARPphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2004-11-02
    Type: Initial release
  • Version 1.1: 2008-04-30
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Derived calculations, Version format compliance
  • Version 1.3: 2021-10-20
    Changes: Database references, Derived calculations
  • Version 1.4: 2024-02-14
    Changes: Data collection