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spinqualitylabelsall models 1f5f, resolution 1.7Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

CRYSTAL STRUCTURE OF THE N-TERMINAL G-DOMAIN OF SHBG IN COMPLEX WITH ZINC

Overview

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.

About this Structure

1F5F is a Single protein structure of sequence from Homo sapiens with CA, ZN, DHT and IPA as ligands. Full crystallographic information is available from OCA.

Reference

Steroid-binding specificity of human sex hormone-binding globulin is influenced by occupancy of a zinc-binding site., Avvakumov GV, Muller YA, Hammond GL, J Biol Chem. 2000 Aug 25;275(34):25920-5. PMID:10859323

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