PDBsum entry 1lhn

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Transport protein PDB id
Jmol PyMol
Protein chain
176 a.a. *
Waters ×88
* Residue conservation analysis
PDB id:
Name: Transport protein
Title: Crystal structure of the n-terminal lg-domain of shbg in complex with 5alpha-androstane-3beta,17alpha-diol
Structure: Sex hormone-binding globulin. Chain: a. Fragment: lg-like 1 domain, residues 30-218. Synonym: shbg, sex steroid-binding protein, sbp, testis- specific androgen-binding protein, abp. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Hexamer (from PDB file)
2.00Å     R-factor:   0.198     R-free:   0.239
Authors: I.Grishkovskaya,G.V.Avvakumov,G.L.Hammond,M.G.Catalano, Y.A.Muller
Key ref:
I.Grishkovskaya et al. (2002). Steroid ligands bind human sex hormone-binding globulin in specific orientations and produce distinct changes in protein conformation. J Biol Chem, 277, 32086-32093. PubMed id: 12065592 DOI: 10.1074/jbc.M203999200
17-Apr-02     Release date:   23-Oct-02    
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Protein chain
Pfam   ArchSchema ?
P04278  (SHBG_HUMAN) -  Sex hormone-binding globulin
402 a.a.
176 a.a.
Key:    PfamA domain  Secondary structure  CATH domain


DOI no: 10.1074/jbc.M203999200 J Biol Chem 277:32086-32093 (2002)
PubMed id: 12065592  
Steroid ligands bind human sex hormone-binding globulin in specific orientations and produce distinct changes in protein conformation.
I.Grishkovskaya, G.V.Avvakumov, G.L.Hammond, M.G.Catalano, Y.A.Muller.
The amino-terminal laminin G-like domain of human sex hormone-binding globulin (SHBG) contains a single high affinity steroid-binding site. Crystal structures of this domain in complex with several different steroid ligands have revealed that estradiol occupies the SHBG steroid-binding site in an opposite orientation when compared with 5 alpha-dihydrotestosterone or C19 androgen metabolites (5 alpha-androstan-3 beta,17 beta-diol and 5 alpha-androstan-3 beta,17 alpha-diol) or the synthetic progestin levonorgestrel. Substitution of specific residues within the SHBG steroid-binding site confirmed that Ser(42) plays a key role in determining high affinity interactions by hydrogen bonding to functional groups at C3 of the androstanediols and levonorgestrel and the hydroxyl at C17 of estradiol. Among residues participating in the hydrogen bond network with hydroxy groups at C17 of C19 steroids or C3 of estradiol, Asp(65) appears to be the most important. The different binding mode of estradiol is associated with a difference in the position/orientation of residues (Leu(131) and Lys(134)) in the loop segment (Leu(131)-His(136)) that covers the steroid-binding site as well as others (Leu(171)-Lys(173) and Trp(84)) on the surface of human SHBG and may provide a basis for ligand-dependent interactions between SHBG and other macromolecules. These new crystal structures have also enabled us to construct a simple space-filling model that can be used to predict the characteristics of novel SHBG ligands.
  Selected figure(s)  
Figure 2.
Fig. 2. Stereo images of the human SHBG steroid-binding site occupied by 3 ,17 Adiol (A), 3 ,17 Adiol (B), and levonorgestrel (C). The orientation of these ligands within the human SHBG steroid-binding site is similar to that observed previously for DHT (8). Images were prepared with Molscript (34) and Raster3d (35).
Figure 3.
Fig. 3. Estradiol binds to human SHBG in an opposite orientation when compared with 3 ,17 Adiol. A, stereo image of the human SHBG steroid-binding site occupied by estradiol. B, superposition of the steroid-binding site in the 3 ,17 Adiol (in blue) and estradiol (in yellow) complexes, illustrating the differences in steroid orientation and coordination. Images were prepared with Molscript (34) and Raster3d (35).
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2002, 277, 32086-32093) copyright 2002.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19744252 K.Yamamoto, E.Koh, F.Matsui, K.Sugimoto, H.S.Sin, Y.Maeda, and M.Namiki (2009).
Measurement-specific bioavailable testosterone using concanavalin A precipitation: comparison of calculated and assayed bioavailable testosterone.
  Int J Urol, 16, 894-901.  
17986201 D.R.Gustafson, C.Karlsson, I.Skoog, L.Rosengren, L.Lissner, and K.Blennow (2007).
Mid-life adiposity factors relate to blood-brain barrier integrity in late life.
  J Intern Med, 262, 643-650.  
17266159 R.Schobert, G.Bernhardt, B.Biersack, S.Bollwein, M.Fallahi, A.Grotemeier, and G.L.Hammond (2007).
Steroid Conjugates of Dichloro(6-aminomethylnicotinate)platinum(II): Effects on DNA, Sex Hormone Binding Globulin, the Estrogen Receptor, and Various Breast Cancer Cell Lines.
  ChemMedChem, 2, 333-342.  
14622020 J.Metzger, A.Schnitzbauer, M.Meyer, M.Söder, C.Y.Cuilleron, H.Hauptmann, E.Huber, and P.B.Luppa (2003).
Binding analysis of 1alpha- and 17alpha-dihydrotestosterone derivatives to homodimeric sex hormone-binding globulin.
  Biochemistry, 42, 13735-13745.  
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