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1xu7

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{{STRUCTURE_1xu7| PDB=1xu7 | SCENE= }}
{{STRUCTURE_1xu7| PDB=1xu7 | SCENE= }}
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'''Crystal Structure of the Interface Open Conformation of Tetrameric 11b-HSD1'''
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===Crystal Structure of the Interface Open Conformation of Tetrameric 11b-HSD1===
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==Overview==
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Human 11beta-hydroxysteroid dehydrogenase type I (11beta-HSD1) is an ER-localized membrane protein that catalyzes the interconversion of cortisone and cortisol. In adipose tissue, excessive cortisol production through 11beta-HSD1 activity has been implicated in the pathogenesis of type II diabetes and obesity. We report here biophysical, kinetic, mutagenesis, and structural data on two ternary complexes of 11beta-HSD1. The combined results reveal flexible active site interactions relevant to glucocorticoid recognition and demonstrate how four 11beta-HSD1 C termini converge to form an as yet uncharacterized tetramerization motif. A C-terminal Pro-Cys motif is localized at the center of the tetramer and forms reversible enzyme disulfides that alter enzyme activity. Conformational flexibility at the tetramerization interface is coupled to structural changes at the enzyme active site suggesting how the central Pro-Cys motif may regulate enzyme activity. Together, the crystallographic and biophysical data provide a structural framework for understanding 11beta-HSD1 activities and will ultimately facilitate the development of specific inhibitors.
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The line below this paragraph, {{ABSTRACT_PUBMED_15513927}}, adds the Publication Abstract to the page
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(as it appears on PubMed at http://www.pubmed.gov), where 15513927 is the PubMed ID number.
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{{ABSTRACT_PUBMED_15513927}}
==About this Structure==
==About this Structure==
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[[Category: Hydroxysteroid]]
[[Category: Hydroxysteroid]]
[[Category: Sdr]]
[[Category: Sdr]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 15:30:57 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 00:33:20 2008''

Revision as of 21:33, 27 July 2008

Image:1xu7.png

Template:STRUCTURE 1xu7

Crystal Structure of the Interface Open Conformation of Tetrameric 11b-HSD1

Template:ABSTRACT PUBMED 15513927

About this Structure

1XU7 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Conformational flexibility in crystal structures of human 11beta-hydroxysteroid dehydrogenase type I provide insights into glucocorticoid interconversion and enzyme regulation., Hosfield DJ, Wu Y, Skene RJ, Hilgers M, Jennings A, Snell GP, Aertgeerts K, J Biol Chem. 2005 Feb 11;280(6):4639-48. Epub 2004 Oct 28. PMID:15513927

Page seeded by OCA on Mon Jul 28 00:33:20 2008

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