1w6k: Difference between revisions
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|PDB= 1w6k |SIZE=350|CAPTION= <scene name='initialview01'>1w6k</scene>, resolution 2.1Å | |PDB= 1w6k |SIZE=350|CAPTION= <scene name='initialview01'>1w6k</scene>, resolution 2.1Å | ||
|SITE= <scene name='pdbsite=AC1:Lan+Binding+Site+For+Chain+A'>AC1</scene> | |SITE= <scene name='pdbsite=AC1:Lan+Binding+Site+For+Chain+A'>AC1</scene> | ||
|LIGAND= <scene name='pdbligand=BOG:B-OCTYLGLUCOSIDE'>BOG</scene> | |LIGAND= <scene name='pdbligand=BOG:B-OCTYLGLUCOSIDE'>BOG</scene>, <scene name='pdbligand=LAN:LANOSTEROL'>LAN</scene> | ||
|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] | |ACTIVITY= <span class='plainlinks'>[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] </span> | ||
|GENE= | |GENE= | ||
|DOMAIN= | |||
|RELATEDENTRY= | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1w6k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1w6k OCA], [http://www.ebi.ac.uk/pdbsum/1w6k PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1w6k RCSB]</span> | |||
}} | }} | ||
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==Overview== | ==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. | 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. | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Schulz-Gasch, T.]] | [[Category: Schulz-Gasch, T.]] | ||
[[Category: Thoma, R.]] | [[Category: Thoma, R.]] | ||
[[Category: b-octyl-glucoside]] | [[Category: b-octyl-glucoside]] | ||
[[Category: cholesterol]] | [[Category: cholesterol]] | ||
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[[Category: steroid biosynthesis]] | [[Category: steroid biosynthesis]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 00:31:51 2008'' | ||
