2rbe: Difference between revisions

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Revision as of 04:58, 31 March 2008

File:2rbe.jpg

, resolution 1.900Å

Ligands:

,

Gene:

HSD11B1, HSD11, HSD11L (Homo sapiens)

Activity:

11-beta-hydroxysteroid dehydrogenase, with EC number 1.1.1.146

Resources:

FirstGlance, OCA, PDBsum, RCSB

Coordinates:

save as pdb, mmCIF, xml

The discovery of 2-anilinothiazolones as 11beta-HSD1 inhibitors

OverviewOverview

A series of 2-anilinothiazolones were prepared as inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1). The most potent compounds contained a 2-chloro or 2-fluoro group on the aniline ring with an isopropyl substituent on the 5-position of the thiazolone ring (compounds 2 and 3, respectively). The binding mode was determined through the X-ray co-crystal structure of the enzyme with compound 3. This compound was also approximately 70-fold selective over 11beta-HSD2 and was orally bioavailable in rat pharmacokinetic studies. However, compound 3 was >580-fold less active in the 11beta-HSD1 cell assay when tested in the presence of 3% human serum albumin.

About this StructureAbout this Structure

2RBE is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

The discovery of 2-anilinothiazolones as 11beta-HSD1 inhibitors., Yuan C, St Jean DJ Jr, Liu Q, Cai L, Li A, Han N, Moniz G, Askew B, Hungate RW, Johansson L, Tedenborg L, Pyring D, Williams M, Hale C, Chen M, Cupples R, Zhang J, Jordan S, Bartberger MD, Sun Y, Emery M, Wang M, Fotsch C, Bioorg Med Chem Lett. 2007 Nov 15;17(22):6056-61. Epub 2007 Sep 25. PMID:17919905

Page seeded by OCA on Mon Mar 31 04:58:34 2008

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

OCA

@@ Line 4: / Line 4: @@
 |PDB= 2rbe |SIZE=350|CAPTION= <scene name='initialview01'>2rbe</scene>, resolution 1.900&Aring;
 |SITE=
-|LIGAND= <scene name='pdbligand=ZMG:'>ZMG</scene> and <scene name='pdbligand=NDP:NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE'>NDP</scene>
+|LIGAND= <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=ZMG:(5R)-2-[(2-FLUOROPHENYL)AMINO]-5-(1-METHYLETHYL)-1,3-THIAZOL-4(5H)-ONE'>ZMG</scene>
-|ACTIVITY= [http://en.wikipedia.org/wiki/11-beta-hydroxysteroid_dehydrogenase 11-beta-hydroxysteroid dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.146 1.1.1.146]
+|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/11-beta-hydroxysteroid_dehydrogenase 11-beta-hydroxysteroid dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.146 1.1.1.146] </span>
 |GENE= HSD11B1, HSD11, HSD11L ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
+|DOMAIN=
+|RELATEDENTRY=
+|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2rbe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2rbe OCA], [http://www.ebi.ac.uk/pdbsum/2rbe PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2rbe RCSB]</span>
 }}
@@ Line 26: / Line 29: @@
 [[Category: Li, V.]]
 [[Category: Zhang, J.]]
-[[Category: NDP]]
-[[Category: ZMG]]
 [[Category: 3-layer(aba) sandwich]]
 [[Category: alpha beta]]
@@ Line 44: / Line 45: @@
 [[Category: transmembrane]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 18:34:24 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:58:34 2008''