1F5F

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

Summary for 1F5F

• Entry DOI: 10.2210/pdb1f5f/pdb
• Related: 1d2s
• Descriptor: SEX HORMONE-BINDING GLOBULIN, CALCIUM ION, ZINC ION, ... (6 entities in total)
• Functional Keywords: jellyroll, signaling protein
• Biological source: Homo sapiens (human)
• Cellular location: Secreted : P04278
• Total number of polymer chains: 1
• Total formula weight: 23132.05

Authors

Avvakumov, V.A.,Muller, Y.A.,Hammond, G.L. (deposition date: 2000-06-14, release date: 2000-09-06, Last modification date: 2024-11-13)

Primary citation

Avvakumov, G.V.,Muller, Y.A.,Hammond, G.L.
Steroid-binding specificity of human sex hormone-binding globulin is influenced by occupancy of a zinc-binding site.
J.Biol.Chem., 275:25920-25925, 2000

PubMed 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.

PubMed: 10859323
DOI: 10.1074/jbc.M004484200

Experimental method

X-RAY DIFFRACTION (1.7 Å)