1XSE

Crystal Structure of Guinea Pig 11beta-Hydroxysteroid Dehydrogenase Type 1


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.267 
  • R-Value Work: 0.192 
  • R-Value Observed: 0.196 

wwPDB Validation   3D Report Full Report


This is version 1.5 of the entry. See complete history


Literature

The crystal structure of guinea pig 11beta-hydroxysteroid dehydrogenase type 1 provides a model for enzyme-lipid bilayer interactions

Ogg, D.Elleby, B.Norstrom, C.Stefansson, K.Abrahmsen, L.Oppermann, U.Svensson, S.

(2005) J Biol Chem 280: 3789-3794

  • DOI: https://doi.org/10.1074/jbc.M412463200
  • Primary Citation of Related Structures:  
    1XSE

  • PubMed Abstract: 

    The metabolic reduction of 11-keto groups in glucocorticoid steroids such as cortisone leads to the nuclear receptor ligand cortisol. This conversion is an example of pre-receptor regulation and constitutes a novel pharmacological target for the treatment of metabolic disorders such as insulin resistance and possibly other derangements observed in the metabolic syndrome, such as hyperlipidemia, hypertension, and lowered insulin secretion. This reaction is carried out by the NADPH-dependent type 1 11beta-hydroxysteroid dehydrogenase (11beta-HSD1), an enzyme attached through an integral N-terminal transmembrane helix to the lipid bilayer and located with its active site within the lumen of the endoplasmic reticulum. Here we report the crystal structure of recombinant guinea pig 11beta-HSD1. This variant was determined in complex with NADP at 2.5 A resolution and crystallized in the presence of detergent and guanidinium hydrochloride. The overall structure of guinea pig 11beta-HSD1 shows a clear relationship to other members of the superfamily of short-chain dehydrogenases/reductases but harbors a unique C-terminal helical segment that fulfills three essential functions and accordingly is involved in subunit interactions, contributes to active site architecture, and is necessary for lipid-membrane interactions. The structure provides a model for enzyme-lipid bilayer interactions and suggests a funneling of lipophilic substrates such as steroid hormones from the hydrophobic membrane environment to the enzyme active site.


  • Organizational Affiliation

    Department of Structural Chemistry, Biovitrum, SE-112 76 Stockholm, Sweden.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
11beta-hydroxysteroid dehydrogenase type 1
A, B
295Cavia porcellusMutation(s): 0 
EC: 1.1.1.146
UniProt
Find proteins for Q6QLL4 (Cavia porcellus)
Explore Q6QLL4 
Go to UniProtKB:  Q6QLL4
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ6QLL4
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
NDP
Query on NDP

Download Ideal Coordinates CCD File 
C [auth A],
D [auth B]
NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE
C21 H30 N7 O17 P3
ACFIXJIJDZMPPO-NNYOXOHSSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.267 
  • R-Value Work: 0.192 
  • R-Value Observed: 0.196 
  • Space Group: I 4 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 118.385α = 90
b = 118.385β = 90
c = 184.772γ = 90
Software Package:
Software NamePurpose
SHARPphasing
REFMACrefinement
DENZOdata reduction
SCALEPACKdata scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2004-11-16
    Type: Initial release
  • Version 1.1: 2008-04-30
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2011-07-27
    Changes: Version format compliance
  • Version 1.4: 2018-08-08
    Changes: Data collection
  • Version 1.5: 2024-03-13
    Changes: Data collection, Database references, Derived calculations, Refinement description