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1xf0

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[[Image:1xf0.gif|left|200px]]
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[[Image:1xf0.png|left|200px]]
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==Overview==
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{{ABSTRACT_15087468}}
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Human type 5 17beta-hydroxysteroid dehydrogenase (17beta-HSD5;AKR1C3) plays a major role in the metabolism of androgens in peripheral tissues. In prostate basal cells, this enzyme is involved in the transformation of dehydroepiandrosterone into dihydrotestosterone, the most potent androgen. It is thus a potential target for prostate cancer therapy because it is understood that the testosterone formation by this enzyme is an important factor, particularly in patients who have undergone surgical or medical castration. Here we report the first structure of a human type 5 17beta-HSD in two ternary complexes, in which we found that the androstenedione molecule has a different binding position from that of testosterone. The two testosterone-binding orientations in the substrate-binding site demonstrate the structural basis of the alternative binding and multispecificity of the enzyme. Phe306 and Trp227 are the key residues involved in ligand recognition as well as product release. A safety belt in the cofactor-binding site enhances nicotinamide adenine dinucleotide phosphate binding and accounts for its high affinity as demonstrated by kinetic studies. These structures have provided a dynamic view of the enzyme reaction converting androstenedione to testosterone as well as valuable information for the development of potent enzyme inhibitors.
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==About this Structure==
==About this Structure==
1XF0 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The following page contains interesting information on the relation of 1XF0 with [[http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb92_1.html Anabolic Steroids]]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XF0 OCA].
1XF0 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The following page contains interesting information on the relation of 1XF0 with [[http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb92_1.html Anabolic Steroids]]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XF0 OCA].
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==Reference==
 
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Crystal structures of the multispecific 17beta-hydroxysteroid dehydrogenase type 5: critical androgen regulation in human peripheral tissues., Qiu W, Zhou M, Labrie F, Lin SX, Mol Endocrinol. 2004 Jul;18(7):1798-807. Epub 2004 Apr 15. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15087468 15087468]
 
[[Category: Anabolic Steroids]]
[[Category: Anabolic Steroids]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Alpha/beta barrel]]
[[Category: Alpha/beta barrel]]
[[Category: Beta-hairpin]]
[[Category: Beta-hairpin]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 14:56:38 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Jun 26 18:06:35 2008''

Revision as of 15:06, 26 June 2008

Image:1xf0.png

Template:STRUCTURE 1xf0

Crystal structure of human 17beta-hydroxysteroid dehydrogenase type 5 (AKR1C3) complexed with delta4-androstene-3,17-dione and NADP


Template:ABSTRACT 15087468

About this Structure

1XF0 is a Single protein structure of sequence from Homo sapiens. The following page contains interesting information on the relation of 1XF0 with [Anabolic Steroids]. Full crystallographic information is available from OCA.

Page seeded by OCA on Thu Jun 26 18:06:35 2008

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