1w6j

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[[Image:1w6j.gif|left|200px]]
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{{Seed}}
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[[Image:1w6j.png|left|200px]]
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{{STRUCTURE_1w6j| PDB=1w6j | SCENE= }}
{{STRUCTURE_1w6j| PDB=1w6j | SCENE= }}
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'''STRUCTURE OF HUMAN OSC IN COMPLEX WITH RO 48-8071'''
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===STRUCTURE OF HUMAN OSC IN COMPLEX WITH RO 48-8071===
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==Overview==
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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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The line below this paragraph, {{ABSTRACT_PUBMED_15525992}}, adds the Publication Abstract to the page
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(as it appears on PubMed at http://www.pubmed.gov), where 15525992 is the PubMed ID number.
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{{ABSTRACT_PUBMED_15525992}}
==About this Structure==
==About this Structure==
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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 13:13:25 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 07:33:20 2008''

Revision as of 04:33, 28 July 2008

Image:1w6j.png

Template:STRUCTURE 1w6j

STRUCTURE OF HUMAN OSC IN COMPLEX WITH RO 48-8071

Template:ABSTRACT PUBMED 15525992

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

Page seeded by OCA on Mon Jul 28 07:33:20 2008

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