2aa5

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[[Image:2aa5.gif|left|200px]]
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{{STRUCTURE_2aa5| PDB=2aa5 | SCENE= }}
{{STRUCTURE_2aa5| PDB=2aa5 | SCENE= }}
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'''Mineralocorticoid Receptor with Bound Progesterone'''
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===Mineralocorticoid Receptor with Bound Progesterone===
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==Overview==
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Ligand binding is the first step in hormone regulation of mineralocorticoid receptor (MR) activity. Here, we report multiple crystal structures of MR (NR3C2) bound to both agonist and antagonists. These structures combined with mutagenesis studies reveal that maximal receptor activation involves an intricate ligand-mediated hydrogen bond network with Asn770 which serves dual roles: stabilization of the loop preceding the C-terminal activation function-2 helix and direct contact with the hormone ligand. In addition, most activating ligands hydrogen bond to Thr945 on helix 10. Structural characterization of the naturally occurring S810L mutant explains how stabilization of a helix 3/helix 5 interaction can circumvent the requirement for this hydrogen bond network. Taken together, these results explain the potency of MR activation by aldosterone, the weak activation induced by progesterone and the antihypertensive agent spironolactone, and the binding selectivity of cortisol over cortisone.
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(as it appears on PubMed at http://www.pubmed.gov), where 15967794 is the PubMed ID number.
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{{ABSTRACT_PUBMED_15967794}}
==About this Structure==
==About this Structure==
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[[Category: Progesterone]]
[[Category: Progesterone]]
[[Category: Steroid receptor]]
[[Category: Steroid receptor]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 18:48:13 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 13:24:39 2008''

Revision as of 10:24, 27 July 2008

Image:2aa5.png

Template:STRUCTURE 2aa5

Mineralocorticoid Receptor with Bound Progesterone

Template:ABSTRACT PUBMED 15967794

About this Structure

2AA5 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

A ligand-mediated hydrogen bond network required for the activation of the mineralocorticoid receptor., Bledsoe RK, Madauss KP, Holt JA, Apolito CJ, Lambert MH, Pearce KH, Stanley TB, Stewart EL, Trump RP, Willson TM, Williams SP, J Biol Chem. 2005 Sep 2;280(35):31283-93. Epub 2005 Jun 20. PMID:15967794

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