3bgl: Difference between revisions
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|PDB= 3bgl |SIZE=350|CAPTION= <scene name='initialview01'>3bgl</scene>, resolution 2.225Å | |PDB= 3bgl |SIZE=350|CAPTION= <scene name='initialview01'>3bgl</scene>, resolution 2.225Å | ||
|SITE= <scene name='pdbsite=AC1:Rid+Binding+Site+For+Residue+A+2'>AC1</scene>, <scene name='pdbsite=AC2:Rid+Binding+Site+For+Residue+B+1'>AC2</scene>, <scene name='pdbsite=AC3:Rid+Binding+Site+For+Residue+C+4'>AC3</scene> and <scene name='pdbsite=AC4:Rid+Binding+Site+For+Residue+D+3'>AC4</scene> | |SITE= <scene name='pdbsite=AC1:Rid+Binding+Site+For+Residue+A+2'>AC1</scene>, <scene name='pdbsite=AC2:Rid+Binding+Site+For+Residue+B+1'>AC2</scene>, <scene name='pdbsite=AC3:Rid+Binding+Site+For+Residue+C+4'>AC3</scene> and <scene name='pdbsite=AC4:Rid+Binding+Site+For+Residue+D+3'>AC4</scene> | ||
|LIGAND= <scene name='pdbligand=RID:'>RID</scene> | |LIGAND= <scene name='pdbligand=RID:(3R,5R)-7-[2-(4-FLUOROPHENYL)-5-(1-METHYLETHYL)-4-(MORPHOLIN-4-YLSULFONYL)-3-PHENYL-1H-PYRROL-1-YL]-3,5-DIHYDROXYHEPTANOIC+ACID'>RID</scene> | ||
|ACTIVITY= [http://en.wikipedia.org/wiki/Hydroxymethylglutaryl-CoA_reductase_(NADPH) Hydroxymethylglutaryl-CoA reductase (NADPH)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.34 1.1.1.34] | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Hydroxymethylglutaryl-CoA_reductase_(NADPH) Hydroxymethylglutaryl-CoA reductase (NADPH)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.34 1.1.1.34] </span> | ||
|GENE= HMGCR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= HMGCR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
|DOMAIN= | |||
|RELATEDENTRY=[[2q1l|2Q1L]], [[2q6b|2Q6B]], [[2q6c|2Q6C]], [[2r4f|2R4F]] | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3bgl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bgl OCA], [http://www.ebi.ac.uk/pdbsum/3bgl PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=3bgl RCSB]</span> | |||
}} | }} | ||
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==Overview== | ==Overview== | ||
4-Sulfamoyl pyrroles were designed as novel hepatoselective HMG-CoA reductase inhibitors (statins) to reduce myalgia, a statin-induced adverse effect. The compounds were prepared via a [3+2] cycloaddition of a Munchnone with a sulfonamide-substituted alkyne. We identified compounds with greater selectivity for hepatocytes compared to L6-myocytes than rosuvastatin and atorvastatin. There was an inverse correlation of myocyte potencies and ClogP values. A number of analogs were effective at reducing cholesterol in acute and chronic in vivo models but they lacked sufficient chronic in vivo activity to warrant further development. | 4-Sulfamoyl pyrroles were designed as novel hepatoselective HMG-CoA reductase inhibitors (statins) to reduce myalgia, a statin-induced adverse effect. The compounds were prepared via a [3+2] cycloaddition of a Munchnone with a sulfonamide-substituted alkyne. We identified compounds with greater selectivity for hepatocytes compared to L6-myocytes than rosuvastatin and atorvastatin. There was an inverse correlation of myocyte potencies and ClogP values. A number of analogs were effective at reducing cholesterol in acute and chronic in vivo models but they lacked sufficient chronic in vivo activity to warrant further development. | ||
==Disease== | |||
Known disease associated with this structure: Statins, attenuated cholesterol lowering by OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=142910 142910]] | |||
==About this Structure== | ==About this Structure== | ||
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[[Category: Park, W K.C.]] | [[Category: Park, W K.C.]] | ||
[[Category: Pavlovsky, A.]] | [[Category: Pavlovsky, A.]] | ||
[[Category: alternative splicing]] | [[Category: alternative splicing]] | ||
[[Category: cholesterol biosynthesis]] | [[Category: cholesterol biosynthesis]] | ||
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[[Category: transmembrane]] | [[Category: transmembrane]] | ||
''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 05:26:02 2008'' | ||