1a28
From Proteopedia
(New page: 200px<br /> <applet load="1a28" size="450" color="white" frame="true" align="right" spinBox="true" caption="1a28, resolution 1.8Å" /> '''HORMONE-BOUND HUMAN ...) |
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| - | [[Image:1a28.gif|left|200px]]<br /> | + | [[Image:1a28.gif|left|200px]]<br /><applet load="1a28" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1a28" size=" | + | |
caption="1a28, resolution 1.8Å" /> | caption="1a28, resolution 1.8Å" /> | ||
'''HORMONE-BOUND HUMAN PROGESTERONE RECEPTOR LIGAND-BINDING DOMAIN'''<br /> | '''HORMONE-BOUND HUMAN PROGESTERONE RECEPTOR LIGAND-BINDING DOMAIN'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The physiological effects of progestins are mediated by the progesterone | + | 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== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1A28 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with STR as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1A28 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=STR:'>STR</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1A28 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Sigler, P | + | [[Category: Sigler, P B.]] |
| - | [[Category: Williams, S | + | [[Category: Williams, S P.]] |
[[Category: STR]] | [[Category: STR]] | ||
[[Category: nuclear receptor]] | [[Category: nuclear receptor]] | ||
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[[Category: transcription regulation]] | [[Category: transcription regulation]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:40:04 2008'' |
Revision as of 09:40, 21 February 2008
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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 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
Page seeded by OCA on Thu Feb 21 11:40:04 2008
