1x8l

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(New page: 200px<br /><applet load="1x8l" size="450" color="white" frame="true" align="right" spinBox="true" caption="1x8l, resolution 2.10&Aring;" /> '''Crystal structure of...)
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[[Image:1x8l.gif|left|200px]]<br /><applet load="1x8l" size="450" color="white" frame="true" align="right" spinBox="true"
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[[Image:1x8l.gif|left|200px]]<br /><applet load="1x8l" size="350" color="white" frame="true" align="right" spinBox="true"
caption="1x8l, resolution 2.10&Aring;" />
caption="1x8l, resolution 2.10&Aring;" />
'''Crystal structure of retinol dehydratase in complex with all-trans-4-oxoretinol and inactive cofactor PAP'''<br />
'''Crystal structure of retinol dehydratase in complex with all-trans-4-oxoretinol and inactive cofactor PAP'''<br />
==Overview==
==Overview==
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The structure of retinol dehydratase (DHR) from Spodoptera frugiperda, a, member of the sulfotransferase superfamily, in complexes with the inactive, form of the cofactor PAP 3'-phosphoadenosine 5'-phosphate (PAP) and (1), the product of the reaction with retinol anhydroretinol (AR), (2) the, retinoid inhibitor all-trans-4-oxoretinol (OR), and (3) the potent steroid, inhibitor androsterone (AND) have been determined and compared to the, enzyme complex with PAP and retinol. The structures show that the geometry, of the active-site amino acids is largely preserved in the various, complexes. However, the beta-ionone rings of the retinoids are oriented, differently with respect to side chains that have been shown to be, important for the enzymatic reaction. In addition, the DHR:PAP:AND complex, reveals a novel mode for steroid binding that contrasts significantly with, that for steroid binding in other sulfotransferases. The molecule is, displaced and rotated approximately 180 degrees along its length so that, there is no acceptor hydroxyl in close proximity to the site of sulfate, transfer. This observation explains why steroids are potent inhibitors of, retinol dehydratase activity, rather than substrates for sulfonation. Most, of the steroid-protein contacts are provided by the alpha-helical cap that, distinguishes this member of the superfamily. This observation suggests, that in addition to providing a chemical environment that promotes the, dehydration of a sulfonated intermediate, the cap may also serve to, minimize a promiscuous sulfotransferases activity.
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The structure of retinol dehydratase (DHR) from Spodoptera frugiperda, a member of the sulfotransferase superfamily, in complexes with the inactive form of the cofactor PAP 3'-phosphoadenosine 5'-phosphate (PAP) and (1) the product of the reaction with retinol anhydroretinol (AR), (2) the retinoid inhibitor all-trans-4-oxoretinol (OR), and (3) the potent steroid inhibitor androsterone (AND) have been determined and compared to the enzyme complex with PAP and retinol. The structures show that the geometry of the active-site amino acids is largely preserved in the various complexes. However, the beta-ionone rings of the retinoids are oriented differently with respect to side chains that have been shown to be important for the enzymatic reaction. In addition, the DHR:PAP:AND complex reveals a novel mode for steroid binding that contrasts significantly with that for steroid binding in other sulfotransferases. The molecule is displaced and rotated approximately 180 degrees along its length so that there is no acceptor hydroxyl in close proximity to the site of sulfate transfer. This observation explains why steroids are potent inhibitors of retinol dehydratase activity, rather than substrates for sulfonation. Most of the steroid-protein contacts are provided by the alpha-helical cap that distinguishes this member of the superfamily. This observation suggests that in addition to providing a chemical environment that promotes the dehydration of a sulfonated intermediate, the cap may also serve to minimize a promiscuous sulfotransferases activity.
==About this Structure==
==About this Structure==
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1X8L is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Spodoptera_frugiperda Spodoptera frugiperda] with HG, CA, A3P and OXR as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1X8L OCA].
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1X8L is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Spodoptera_frugiperda Spodoptera frugiperda] with <scene name='pdbligand=HG:'>HG</scene>, <scene name='pdbligand=CA:'>CA</scene>, <scene name='pdbligand=A3P:'>A3P</scene> and <scene name='pdbligand=OXR:'>OXR</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1X8L OCA].
==Reference==
==Reference==
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[[Category: Spodoptera frugiperda]]
[[Category: Spodoptera frugiperda]]
[[Category: Buck, J.]]
[[Category: Buck, J.]]
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[[Category: Newcomer, M.E.]]
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[[Category: Newcomer, M E.]]
[[Category: Pakhomova, S.]]
[[Category: Pakhomova, S.]]
[[Category: A3P]]
[[Category: A3P]]
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[[Category: sulfotransferase]]
[[Category: sulfotransferase]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Sun Nov 25 01:38:16 2007''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:52:12 2008''

Revision as of 13:52, 21 February 2008

Image:1x8l.gif

1x8l, resolution 2.10Å

Drag the structure with the mouse to rotate

Crystal structure of retinol dehydratase in complex with all-trans-4-oxoretinol and inactive cofactor PAP

Overview

The structure of retinol dehydratase (DHR) from Spodoptera frugiperda, a member of the sulfotransferase superfamily, in complexes with the inactive form of the cofactor PAP 3'-phosphoadenosine 5'-phosphate (PAP) and (1) the product of the reaction with retinol anhydroretinol (AR), (2) the retinoid inhibitor all-trans-4-oxoretinol (OR), and (3) the potent steroid inhibitor androsterone (AND) have been determined and compared to the enzyme complex with PAP and retinol. The structures show that the geometry of the active-site amino acids is largely preserved in the various complexes. However, the beta-ionone rings of the retinoids are oriented differently with respect to side chains that have been shown to be important for the enzymatic reaction. In addition, the DHR:PAP:AND complex reveals a novel mode for steroid binding that contrasts significantly with that for steroid binding in other sulfotransferases. The molecule is displaced and rotated approximately 180 degrees along its length so that there is no acceptor hydroxyl in close proximity to the site of sulfate transfer. This observation explains why steroids are potent inhibitors of retinol dehydratase activity, rather than substrates for sulfonation. Most of the steroid-protein contacts are provided by the alpha-helical cap that distinguishes this member of the superfamily. This observation suggests that in addition to providing a chemical environment that promotes the dehydration of a sulfonated intermediate, the cap may also serve to minimize a promiscuous sulfotransferases activity.

About this Structure

1X8L is a Single protein structure of sequence from Spodoptera frugiperda with , , and as ligands. Full crystallographic information is available from OCA.

Reference

The structures of the unique sulfotransferase retinol dehydratase with product and inhibitors provide insight into enzyme mechanism and inhibition., Pakhomova S, Buck J, Newcomer ME, Protein Sci. 2005 Jan;14(1):176-82. Epub 2004 Dec 2. PMID:15608121

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