1FDV

HUMAN 17-BETA-HYDROXYSTEROID-DEHYDROGENASE TYPE 1 MUTANT H221L COMPLEXED WITH NAD+


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.10 Å
  • R-Value Free: 0.295 
  • R-Value Work: 0.219 

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Ligand Structure Quality Assessment 


This is version 1.6 of the entry. See complete history


Literature

Unusual charge stabilization of NADP+ in 17beta-hydroxysteroid dehydrogenase.

Mazza, C.Breton, R.Housset, D.Fontecilla-Camps, J.C.

(1998) J Biol Chem 273: 8145-8152

  • DOI: https://doi.org/10.1074/jbc.273.14.8145
  • Primary Citation of Related Structures:  
    1FDU, 1FDV, 1FDW

  • PubMed Abstract: 

    Type 1 17beta-hydroxysteroid dehydrogenase (17beta-HSD1), a member of the short chain dehydrogenase reductase (SDR) family, is responsible for the synthesis of 17beta-estradiol, the biologically active estrogen involved in the genesis and development of human breast cancers. Here, we report the crystal structures of the H221L 17beta-HSD1 mutant complexed to NADP+ and estradiol and the H221L mutant/NAD+ and a H221Q mutant/estradiol complexes. These structures provide a complete picture of the NADP+-enzyme interactions involving the flexible 191-199 loop (well ordered in the H221L mutant) and suggest that the hydrophobic residues Phe192-Met193 could facilitate hydride transfer. 17beta-HSD1 appears to be unique among the members of the SDR protein family in that one of the two basic residues involved in the charge compensation of the 2'-phosphate does not belong to the Rossmann-fold motif. The remarkable stabilization of the NADP+ 2'-phosphate by the enzyme also clearly establishes its preference for this cofactor relative to NAD+. Analysis of the catalytic properties of, and estradiol binding to, the two mutants suggests that the His221-steroid O3 hydrogen bond plays an important role in substrate specificity.


  • Organizational Affiliation

    Laboratoire de Cristallographie et Cristallogenèse des Protéines, Institut de Biologie Structurale J.-P. Ebel, CEA-CNRS, 41, avenue des Martyrs, F-38027 Grenoble cedex, France.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
17-BETA-HYDROXYSTEROID DEHYDROGENASE
A, B, C, D
327Homo sapiensMutation(s): 1 
EC: 1.1.1.62
UniProt & NIH Common Fund Data Resources
Find proteins for P14061 (Homo sapiens)
Explore P14061 
Go to UniProtKB:  P14061
PHAROS:  P14061
GTEx:  ENSG00000108786 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP14061
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.10 Å
  • R-Value Free: 0.295 
  • R-Value Work: 0.219 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 115.12α = 90
b = 79.11β = 91.93
c = 120.47γ = 90
Software Package:
Software NamePurpose
AMoREphasing
REFMACrefinement
XDSdata reduction

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 1998-05-27
    Type: Initial release
  • Version 1.1: 2008-03-24
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2018-04-04
    Changes: Data collection
  • Version 1.4: 2018-04-11
    Changes: Data collection
  • Version 1.5: 2021-11-03
    Changes: Database references, Derived calculations
  • Version 1.6: 2023-08-09
    Changes: Refinement description