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PDBsum entry 1kdm

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protein ligands metals links
Transport protein PDB id
1kdm
Jmol
Contents
Protein chain
177 a.a. *
Ligands
DHT
Metals
_CA
Waters ×72
* Residue conservation analysis
PDB id:
1kdm
Name: Transport protein
Title: The crystal structure of the human sex hormone-binding globulin (tetragonal crystal form)
Structure: Sex hormone-binding globulin. Chain: a. Fragment: n-terminal lg-domain. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PDB file)
Resolution:
2.35Å     R-factor:   0.193     R-free:   0.264
Authors: I.Grishkovskaya,G.V.Avvakumov,G.L.Hammond,Y.A.Muller
Key ref:
I.Grishkovskaya et al. (2002). Resolution of a disordered region at the entrance of the human sex hormone-binding globulin steroid-binding site. J Mol Biol, 318, 621-626. PubMed id: 12054810 DOI: 10.1016/S0022-2836(02)00169-9
Date:
13-Nov-01     Release date:   15-May-02    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
P04278  (SHBG_HUMAN) -  Sex hormone-binding globulin
Seq:
Struc:
402 a.a.
177 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 

 
DOI no: 10.1016/S0022-2836(02)00169-9 J Mol Biol 318:621-626 (2002)
PubMed id: 12054810  
 
 
Resolution of a disordered region at the entrance of the human sex hormone-binding globulin steroid-binding site.
I.Grishkovskaya, G.V.Avvakumov, G.L.Hammond, Y.A.Muller.
 
  ABSTRACT  
 
The crystal structure of human sex hormone-binding globulin (SHBG) has revealed how 5alpha-dihydrotestosterone intercalates between the two seven-stranded beta-sheets of its amino-terminal laminin G-like domain. However, a region of disorder (residues 130 to 135 of SHBG) was identified together with a zinc-binding site in immediate proximity to the steroid. It has been important to resolve the structure of this region because previous studies have suggested that these residues may contribute to steroid binding directly. Here, we present the 2.35 A and 1.7 A crystal structures of the amino-terminal LG domain of SHBG obtained from a tetragonal crystal form and by EDTA-soaking of a trigonal crystal form, respectively. In both of these new structures, residues Pro130 to Arg135 are now clearly visible. Substitution of the two residues (Leu131Gly and Lys134Ala) pointing towards the steroid has shown that only Leu131 contributes significantly to steroid binding. Rather than covering the steroid-binding pocket in an extended conformation, a 3(10) helical turn is formed by residues Leu131 to Lys134 in this segment. Unfolding of this secondary structure element can either facilitate the entry of the steroids into the binding site or modulate the important contribution that Leu131 makes to steroid binding. A comparison with previous structures supports the concept that zinc binding re-orients the side-chain of His136, and this residue serves as a lever causing disorder within the loop structure between Pro130 and Arg135.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. Comparison of the SHBG steroid-binding site structure in the presence or in the absence of zinc. (a) The s[a]-weighted 2F[o] -F[c] electron density for the loop segment 130 to 137 in the tetragonal crystal form calculated at 2.35 Å resolution and contoured at 0.9s. Only electron density within 2.5 Å of the displayed atoms is shown. (b) Stereorepresentation of the steroid-binding site of SHBG in the EDTA-soaked crystals obtained at 1.7 Å resolution. The loop segment 130 to 135 is clearly visible and adopts a 3[10] helical turn characterized by a main-chain to main-chain hydrogen bond between Leu131 and Lys134. The side-chain of Lys134 makes a hydrogen bond to the 17b-hydroxy group of DHT. The steroid is shown in a ball and stick representation (yellow and green). Protein main-chain discontinuities are indicated by black spheres. (c) Stereorepresentation of the steroid-binding site of SHBG obtained previously with trigonal crystals in the presence of zinc (PDB accession code 1F5F). Zinc does not bind to a preformed binding site, and zinc binding causes the reorientation of the side-chains of residues Asp65, His83 and His136. As a result, we propose that the reorientation of residue His136 causes disorder of the loop segment (broken line). The Figure was prepared with MOLSCRIPT[13.] and Raster3d. [14.]
 
  The above figure is reprinted by permission from Elsevier: J Mol Biol (2002, 318, 621-626) copyright 2002.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
16601122 K.M.Ng, M.G.Catalano, T.Pinós, D.M.Selva, G.V.Avvakumov, F.Munell, and G.L.Hammond (2006).
Evidence that fibulin family members contribute to the steroid-dependent extravascular sequestration of sex hormone-binding globulin.
  J Biol Chem, 281, 15853-15861.  
12228253 G.V.Avvakumov, I.Grishkovskaya, Y.A.Muller, and G.L.Hammond (2002).
Crystal structure of human sex hormone-binding globulin in complex with 2-methoxyestradiol reveals the molecular basis for high affinity interactions with C-2 derivatives of estradiol.
  J Biol Chem, 277, 45219-45225.
PDB code: 1lhw
12065592 I.Grishkovskaya, G.V.Avvakumov, G.L.Hammond, M.G.Catalano, and Y.A.Muller (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.
PDB codes: 1lhn 1lho 1lhu 1lhv
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