PDBsum entry 1f5f

Signaling protein

PDB id: 1f5f

Contents

Protein chain

172 a.a. *

Ligands

DHT

IPA

Metals

_CA

_ZN ×2

Waters ×130

* Residue conservation analysis

PDB id:

1f5f

Name:

Signaling protein

Title:

Crystal structure of the n-terminal g-domain of shbg in complex with zinc

Structure:

Sex hormone-binding globulin. Chain: a. Fragment: n-terminal fragment of shbg (residues 1 to 205). Synonym: shbg. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Hexamer (from PDB file)

Resolution:

1.70Å R-factor: 0.197 R-free: 0.259

Authors:

V.A.Avvakumov,Y.A.Muller,G.L.Hammond

Key ref:

G.V.Avvakumov et al. (2000). Steroid-binding specificity of human sex hormone-binding globulin is influenced by occupancy of a zinc-binding site. J Biol Chem, 275, 25920-25925. PubMed id: 10859323 DOI: 10.1074/jbc.M004484200

Date:

14-Jun-00 Release date: 06-Sep-00

Protein chain

P04278  (SHBG_HUMAN) -  Sex hormone-binding globulin from Homo sapiens

Seq: 402 a.a.

Struc: 172 a.a.

DOI no: 10.1074/jbc.M004484200

J Biol Chem 275:25920-25925 (2000)

PubMed id: 10859323

Steroid-binding specificity of human sex hormone-binding globulin is influenced by occupancy of a zinc-binding site.

G.V.Avvakumov, Y.A.Muller, G.L.Hammond.

ABSTRACT

One calcium-binding site (site I) and a second poorly defined metal-binding site (site II) have been observed previously within the amino-terminal laminin G-like domain (G domain) of human sex hormone-binding globulin (SHBG). By soaking crystals of this structure in 2.5 mm ZnCl(2), site II and a new metal-binding site (site III) were found to bind Zn(2+). Site II is located close to the steroid-binding site, and Zn(2+) is coordinated by the side chains of His(83) and His(136) and the carboxylate group of Asp(65). In this site, Zn(2+) prevents Asp(65) from interacting with the steroid 17beta-hydroxy group and alters the conformations of His(83) and His(136), as well as a disordered region over the steroid-binding site. Site III is formed by the side chains of His(101) and the carboxylate group of Asp(117), and the distance between them (2.7 A) is increased to 3.7 A in the presence of Zn(2+). The affinity of SHBG for estradiol is reduced in the presence of 0. 1-1 mm Zn(2+), whereas its affinity for androgens is unchanged, and chemically-related metal ions (Cd(2+) and Hg(2+)) have similar but less pronounced effects. This is not observed when Zn(2+) coordination at site II is modified by substituting Gln for His(136). An alteration in the steroid-binding specificity of human SHBG by Zn(2+) occupancy of site II may be relevant in male reproductive tissues where zinc concentrations are very high.

Selected figure(s)

Figure 1.
Fig. 1. Metal-binding sites in the amino-terminal G domain of SHBG. Of the 205 residues of SHBG crystallized, residues 13-131 and 136-188 are visible in the electron density. The steroid DHT is in a ball and stick representation, whereas the calcium-binding site (site I) and the zinc-bindings sites (sites II and III) are shown by white and black spheres, respectively. The figure was prepared with the program MOLSCRIPT (36).

Figure 6.
Fig. 6. Proposed structural rearrangements in the proximity of the steroid-binding site of human SHBG in the presence (A) and absence (B) of Zn2+ in metal-binding site II. The model of the unoccupied metal-binding site II (B) is based on a subtraction of the unambiguous conformations observed for Asp65 and His83 in the presence of zinc (A) from the alternative conformations of these residues observed when metal-binding site II was partially occupied (see Fig. 2B). Note that neither the crystallographic analysis nor the hydrogen bonding network in which Asn82 participates allow us to distinguish whether its nitrogen or oxygen atom points toward the steroid 17 -hydroxy group.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2000, 275, 25920-25925) copyright 2000.

Figures were selected by an automated process.