2r4f

From Proteopedia

(Difference between revisions)

Revision as of 10:54, 5 September 2018

Substituted Pyrazoles as Hepatselective HMG-COA reductase inhibitors

Structural highlights

2r4f is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	2q1l, 2q6b, 2q6c, 3bgl
Gene:	HMGCR (HUMAN)
Activity:	Hydroxymethylglutaryl-CoA reductase (NADPH), with EC number 1.1.1.34
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[HMDH_HUMAN] Transmembrane glycoprotein that is the rate-limiting enzyme in cholesterol biosynthesis as well as in the biosynthesis of nonsterol isoprenoids that are essential for normal cell function including ubiquinone and geranylgeranyl proteins.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

In light of accumulating evidence that aggressive LDL-lowering therapy may offer increased protection against coronary heart disease, we undertook the design and synthesis of a novel series of HMG-CoA reductase inhibitors based upon a substituted pyrazole template. Optimizing this series using both structure-based design and molecular property considerations afforded a class of highly efficacious and hepatoselective inhibitors resulting in the identification of (3 R,5 R)-7-[2-(4-fluoro-phenyl)-4-isopropyl-5-(4-methyl-benzylcarbamoyl)-2 H-pyrazol-3-yl]-3,5-dihydroxy-heptanoic (PF-3052334) as a candidate for the treatment of hypercholesterolemia.

Substituted pyrazoles as hepatoselective HMG-CoA reductase inhibitors: discovery of (3R,5R)-7-[2-(4-fluoro-phenyl)-4-isopropyl-5-(4-methyl-benzylcarbamoyl)-2H -pyrazol-3-yl]-3,5-dihydroxyheptanoic acid (PF-3052334) as a candidate for the treatment of hypercholesterolemia.,Pfefferkorn JA, Choi C, Larsen SD, Auerbach B, Hutchings R, Park W, Askew V, Dillon L, Hanselman JC, Lin Z, Lu GH, Robertson A, Sekerke C, Harris MS, Pavlovsky A, Bainbridge G, Caspers N, Kowala M, Tait BD J Med Chem. 2008 Jan 10;51(1):31-45. Epub 2007 Dec 12. PMID:18072721^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Pfefferkorn JA, Choi C, Larsen SD, Auerbach B, Hutchings R, Park W, Askew V, Dillon L, Hanselman JC, Lin Z, Lu GH, Robertson A, Sekerke C, Harris MS, Pavlovsky A, Bainbridge G, Caspers N, Kowala M, Tait BD. Substituted pyrazoles as hepatoselective HMG-CoA reductase inhibitors: discovery of (3R,5R)-7-[2-(4-fluoro-phenyl)-4-isopropyl-5-(4-methyl-benzylcarbamoyl)-2H -pyrazol-3-yl]-3,5-dihydroxyheptanoic acid (PF-3052334) as a candidate for the treatment of hypercholesterolemia. J Med Chem. 2008 Jan 10;51(1):31-45. Epub 2007 Dec 12. PMID:18072721 doi:10.1021/jm070849r

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2r4f"

@@ Line 1: / Line 1: @@
 ==Substituted Pyrazoles as Hepatselective HMG-COA reductase inhibitors==
 <StructureSection load='2r4f' size='340' side='right' caption='[[2r4f]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
@@ Line 7: / Line 8: @@
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HMGCR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2r4f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2r4f OCA], [http://pdbe.org/2r4f PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2r4f RCSB], [http://www.ebi.ac.uk/pdbsum/2r4f PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2r4f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2r4f OCA], [http://pdbe.org/2r4f PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2r4f RCSB], [http://www.ebi.ac.uk/pdbsum/2r4f PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2r4f ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 15: / Line 16: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/r4/2r4f_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/r4/2r4f_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
-</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2r4f ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 42: / Line 43: @@
 [[Category: Pavlovsky, A]]
 [[Category: Pfefferkorn, J A]]
+[[Category: Alternative splicing]]
 [[Category: Biocynthesis]]
 [[Category: Cholesterol]]
@@ Line 53: / Line 55: @@
 [[Category: Oxidoreductase]]
 [[Category: Peroxisome]]
+[[Category: Polymorphism]]
 [[Category: Statin]]
 [[Category: Steroid biosynthesis]]
 [[Category: Sterol biosynthesis]]
 [[Category: Transmembrane]]

2r4f

From Proteopedia

Revision as of 10:54, 5 September 2018

Substituted Pyrazoles as Hepatselective HMG-COA reductase inhibitors

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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