1LHN: Crystal Structure Of The N-Terminal Lg-Domain Of Shbg In Complex With 5alpha-Androstane-3beta,17alpha-Diol

Citation:
Abstract
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.
PDB ID: 1LHNDownload
MMDB ID: 20903
PDB Deposition Date: 2002/4/17
Updated in MMDB: 2012/11
Experimental Method:
x-ray diffraction
Resolution: 2  Å
Source Organism:
Similar Structures:
Biological Unit for 1LHN: dimeric; determined by author
Molecular Components in 1LHN
Label Count Molecule
Proteins (2 molecules)
2
SEX Hormone-binding Globulin(Gene symbol: SHBG)
Molecule annotation
Chemicals (6 molecules)
1
2
2
2
3
2
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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