1lho

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Revision as of 15:54, 12 November 2007

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spinqualitylabelsall models 1lho, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

CRYSTAL STRUCTURE OF THE N-TERMINAL LG-DOMAIN OF SHBG IN COMPLEX WITH 5ALPHA-ANDROSTANE-3BETA,17BETA-DIOL

Overview

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.

About this Structure

1LHO is a Single protein structure of sequence from Homo sapiens with CA and AOM as ligands. Full crystallographic information is available from OCA.

Reference

Steroid ligands bind human sex hormone-binding globulin in specific orientations and produce distinct changes in protein conformation., Grishkovskaya I, Avvakumov GV, Hammond GL, Catalano MG, Muller YA, J Biol Chem. 2002 Aug 30;277(35):32086-93. Epub 2002 Jun 13. PMID:12065592

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