3bgl: Difference between revisions

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Revision as of 19:58, 20 March 2008

File:3bgl.jpg

, resolution 2.225Å

Sites:

, , and

Ligands:

Gene:

HMGCR (Homo sapiens)

Activity:

Hydroxymethylglutaryl-CoA reductase (NADPH), with EC number 1.1.1.34

Coordinates:

save as pdb, mmCIF, xml

Hepatoselectivity of Statins: Design and synthesis of 4-sulfamoyl pyrroles as HMG-CoA reductase inhibitors

OverviewOverview

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.

About this StructureAbout this Structure

3BGL is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

Hepatoselectivity of statins: design and synthesis of 4-sulfamoyl pyrroles as HMG-CoA reductase inhibitors., Park WK, Kennedy RM, Larsen SD, Miller S, Roth BD, Song Y, Steinbaugh BA, Sun K, Tait BD, Kowala MC, Trivedi BK, Auerbach B, Askew V, Dillon L, Hanselman JC, Lin Z, Lu GH, Robertson A, Sekerke C, Bioorg Med Chem Lett. 2008 Feb 1;18(3):1151-6. Epub 2007 Dec 5. PMID:18155906

Page seeded by OCA on Thu Mar 20 18:58:44 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-[[Image:3bgl.jpg|left|200px]]<br /><applet load="3bgl" size="350" color="white" frame="true" align="right" spinBox="true"
+[[Image:3bgl.jpg|left|200px]]
-caption="3bgl, resolution 2.225&Aring;" />
-'''Hepatoselectivity of Statins: Design and synthesis of 4-sulfamoyl pyrroles as HMG-CoA reductase inhibitors'''<br />
+ {{Structure
+|PDB= 3bgl |SIZE=350|CAPTION= <scene name='initialview01'>3bgl</scene>, resolution 2.225&Aring;
+|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>
+|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]
+|GENE= HMGCR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
+}}
+'''Hepatoselectivity of Statins: Design and synthesis of 4-sulfamoyl pyrroles as HMG-CoA reductase inhibitors'''
 ==Overview==
@@ Line 7: / Line 16: @@
 ==About this Structure==
-BGL is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=RID:'>RID</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Known structural/functional Sites: <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>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BGL OCA].
+BGL 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=3BGL OCA].
 ==Reference==
-Hepatoselectivity of statins: design and synthesis of 4-sulfamoyl pyrroles as HMG-CoA reductase inhibitors., Park WK, Kennedy RM, Larsen SD, Miller S, Roth BD, Song Y, Steinbaugh BA, Sun K, Tait BD, Kowala MC, Trivedi BK, Auerbach B, Askew V, Dillon L, Hanselman JC, Lin Z, Lu GH, Robertson A, Sekerke C, Bioorg Med Chem Lett. 2008 Feb 1;18(3):1151-6. Epub 2007 Dec 5. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=18155906 18155906]
+Hepatoselectivity of statins: design and synthesis of 4-sulfamoyl pyrroles as HMG-CoA reductase inhibitors., Park WK, Kennedy RM, Larsen SD, Miller S, Roth BD, Song Y, Steinbaugh BA, Sun K, Tait BD, Kowala MC, Trivedi BK, Auerbach B, Askew V, Dillon L, Hanselman JC, Lin Z, Lu GH, Robertson A, Sekerke C, Bioorg Med Chem Lett. 2008 Feb 1;18(3):1151-6. Epub 2007 Dec 5. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18155906 18155906]
 [[Category: Homo sapiens]]
 [[Category: Hydroxymethylglutaryl-CoA reductase (NADPH)]]
@@ Line 33: / Line 42: @@
 [[Category: transmembrane]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 19:05:35 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 18:58:44 2008''