1w6k

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[[Image:1w6k.gif|left|200px]]
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[[Image:1w6k.png|left|200px]]
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==Overview==
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{{ABSTRACT_15525992}}
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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.
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==About this Structure==
==About this Structure==
1W6K 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=1W6K OCA].
1W6K 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=1W6K OCA].
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==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://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: Monotopic membrane protein]]
[[Category: Monotopic membrane protein]]
[[Category: Steroid biosynthesis]]
[[Category: Steroid biosynthesis]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 13:13:33 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Jun 26 18:05:51 2008''

Revision as of 15:05, 26 June 2008

Image:1w6k.png

Template:STRUCTURE 1w6k

STRUCTURE OF HUMAN OSC IN COMPLEX WITH LANOSTEROL


Template:ABSTRACT 15525992

About this Structure

1W6K is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Page seeded by OCA on Thu Jun 26 18:05:51 2008

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