1gsz
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Squalene-hopene cyclase (SHC) catalyzes the conversion of squalene into | + | Squalene-hopene cyclase (SHC) catalyzes the conversion of squalene into pentacyclic compounds. It is the prokaryotic counterpart of the eukaryotic oxidosqualene cyclase (OSC) that catalyzes the steroid scaffold formation. Because of clear sequence homology, SHC can serve as a model for OSC, which is an attractive target for anticholesteremic drugs. We have established the crystal structure of SHC complexed with Ro48-8071, a potent inhibitor of OSC and therefore of cholesterol biosynthesis. Ro48-8071 is bound in the active-center cavity of SHC and extends into the channel that connects the cavity with the membrane. The binding site of Ro48-8071 is largely identical with the expected site of squalene; it differs from a previous model based on photoaffinity labeling. The knowledge of the inhibitor binding mode in SHC is likely to help develop more potent inhibitors for OSC. |
==About this Structure== | ==About this Structure== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Lenhart, A.]] | [[Category: Lenhart, A.]] | ||
| - | [[Category: Pleschke, A | + | [[Category: Pleschke, A E.W.]] |
| - | [[Category: Schulz, G | + | [[Category: Schulz, G E.]] |
| - | [[Category: Weihofen, W | + | [[Category: Weihofen, W A.]] |
[[Category: C8E]] | [[Category: C8E]] | ||
[[Category: R71]] | [[Category: R71]] | ||
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[[Category: oxidosqualene cyclase]] | [[Category: oxidosqualene cyclase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:53:35 2008'' |
Revision as of 10:53, 21 February 2008
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CRYSTAL STRUCTURE OF A SQUALENE CYCLASE IN COMPLEX WITH THE POTENTIAL ANTICHOLESTEREMIC DRUG RO48-8071
Overview
Squalene-hopene cyclase (SHC) catalyzes the conversion of squalene into pentacyclic compounds. It is the prokaryotic counterpart of the eukaryotic oxidosqualene cyclase (OSC) that catalyzes the steroid scaffold formation. Because of clear sequence homology, SHC can serve as a model for OSC, which is an attractive target for anticholesteremic drugs. We have established the crystal structure of SHC complexed with Ro48-8071, a potent inhibitor of OSC and therefore of cholesterol biosynthesis. Ro48-8071 is bound in the active-center cavity of SHC and extends into the channel that connects the cavity with the membrane. The binding site of Ro48-8071 is largely identical with the expected site of squalene; it differs from a previous model based on photoaffinity labeling. The knowledge of the inhibitor binding mode in SHC is likely to help develop more potent inhibitors for OSC.
About this Structure
1GSZ is a Single protein structure of sequence from Alicyclobacillus acidocaldarius with and as ligands. Known structural/functional Site: . Full crystallographic information is available from OCA.
Reference
Crystal structure of a squalene cyclase in complex with the potential anticholesteremic drug Ro48-8071., Lenhart A, Weihofen WA, Pleschke AE, Schulz GE, Chem Biol. 2002 May;9(5):639-45. PMID:12031670
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