1w6j

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[[Image:1w6j.gif|left|200px]]<br /><applet load="1w6j" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:1w6j.gif|left|200px]]
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caption="1w6j, resolution 2.20&Aring;" />
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'''STRUCTURE OF HUMAN OSC IN COMPLEX WITH RO 48-8071'''<br />
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{{Structure
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|PDB= 1w6j |SIZE=350|CAPTION= <scene name='initialview01'>1w6j</scene>, resolution 2.20&Aring;
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|SITE= <scene name='pdbsite=AC1:Bog+Binding+Site+For+Chain+A'>AC1</scene>
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|LIGAND= <scene name='pdbligand=BOG:B-OCTYLGLUCOSIDE'>BOG</scene>, <scene name='pdbligand=R71:[4-({6-[ALLYL(METHYL)AMINO]HEXYL}OXY)-2-FLUOROPHENYL](4-BROMOPHENYL)METHANONE'>R71</scene> and <scene name='pdbligand=C14:TETRADECANE'>C14</scene>
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|ACTIVITY= [http://en.wikipedia.org/wiki/Lanosterol_synthase Lanosterol synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.4.99.7 5.4.99.7]
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|GENE=
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}}
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'''STRUCTURE OF HUMAN OSC IN COMPLEX WITH RO 48-8071'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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1W6J 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=BOG:'>BOG</scene>, <scene name='pdbligand=R71:'>R71</scene> and <scene name='pdbligand=C14:'>C14</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Lanosterol_synthase Lanosterol synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.4.99.7 5.4.99.7] Known structural/functional Site: <scene name='pdbsite=AC1:Bog+Binding+Site+For+Chain+A'>AC1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1W6J OCA].
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1W6J is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1W6J OCA].
==Reference==
==Reference==
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Insight into steroid scaffold formation from the structure of human oxidosqualene cyclase., Thoma R, Schulz-Gasch T, D'Arcy B, Benz J, Aebi J, Dehmlow H, Hennig M, Stihle M, Ruf A, Nature. 2004 Nov 4;432(7013):118-22. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15525992 15525992]
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Insight into steroid scaffold formation from the structure of human oxidosqualene cyclase., Thoma R, Schulz-Gasch T, D'Arcy B, Benz J, Aebi J, Dehmlow H, Hennig M, Stihle M, Ruf A, Nature. 2004 Nov 4;432(7013):118-22. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15525992 15525992]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Lanosterol synthase]]
[[Category: Lanosterol synthase]]
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[[Category: steroid biosynthesis]]
[[Category: steroid biosynthesis]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:40:57 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 14:52:52 2008''

Revision as of 12:52, 20 March 2008

Image:1w6j.gif


PDB ID 1w6j

Drag the structure with the mouse to rotate
, resolution 2.20Å
Sites:
Ligands: , and
Activity: Lanosterol synthase, with EC number 5.4.99.7
Coordinates: save as pdb, mmCIF, xml



STRUCTURE OF HUMAN OSC IN COMPLEX WITH RO 48-8071


Contents

Overview

In higher organisms the formation of the steroid scaffold is catalysed exclusively by the membrane-bound oxidosqualene cyclase (OSC; lanosterol synthase). In a highly selective cyclization reaction OSC forms lanosterol with seven chiral centres starting from the linear substrate 2,3-oxidosqualene. Valuable data on the mechanism of the complex cyclization cascade have been collected during the past 50 years using suicide inhibitors, mutagenesis studies and homology modelling. Nevertheless it is still not fully understood how the enzyme catalyses the reaction. Because of the decisive role of OSC in cholesterol biosynthesis it represents a target for the discovery of novel anticholesteraemic drugs that could complement the widely used statins. Here we present two crystal structures of the human membrane protein OSC: the target protein with an inhibitor that showed cholesterol lowering in vivo opens the way for the structure-based design of new OSC inhibitors. The complex with the reaction product lanosterol gives a clear picture of the way in which the enzyme achieves product specificity in this highly exothermic cyclization reaction.

Disease

Known disease associated with this structure: Osteopathia striata with cranial sclerosis OMIM:[300373]

About this Structure

1W6J is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Insight into steroid scaffold formation from the structure of human oxidosqualene cyclase., Thoma R, Schulz-Gasch T, D'Arcy B, Benz J, Aebi J, Dehmlow H, Hennig M, Stihle M, Ruf A, Nature. 2004 Nov 4;432(7013):118-22. PMID:15525992

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