1a28

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1a28, resolution 1.8Å

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HORMONE-BOUND HUMAN PROGESTERONE RECEPTOR LIGAND-BINDING DOMAIN

Contents

Overview

The physiological effects of progestins are mediated by the progesterone, receptor, a member of the steroid/nuclear receptor superfamily. As, progesterone is required for maintenance of pregnancy, its receptor has, been a target for pharmaceuticals. Here we report the 1.8 A crystal, structure of a progesterone-bound ligand-binding domain of the human, progesterone receptor. The nature of this structure explains the, receptor's selective affinity for progestins and establishes a common mode, of recognition of 3-oxy steroids by the cognate receptors. Although the, overall fold of the progesterone receptor is similar to that found in, related receptors, the progesterone receptor has a quite different mode of, dimerization. A hormone-induced stabilization of the carboxy-terminal, secondary structure of the ligand-binding domain of the progesterone, receptor accounts for the stereochemistry of this distinctive dimer, explains the receptor's characteristic pattern of ligand-dependent, protease resistance and its loss of repression, and indicates how the, anti-progestin RU486 might work in birth control. The structure also, indicates that the analogous 3-keto-steroid receptors may have a similar, mechanism of action.

Disease

Known disease associated with this structure: Progesterone resistance, 264080 (2) OMIM:[607311]

About this Structure

1A28 is a Single protein structure of sequence from Homo sapiens with STR as ligand. Full crystallographic information is available from OCA.

Reference

Atomic structure of progesterone complexed with its receptor., Williams SP, Sigler PB, Nature. 1998 May 28;393(6683):392-6. PMID:9620806

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