3frj

From Proteopedia

(Difference between revisions)

Revision as of 07:22, 5 December 2018

Crystal Structure of 11b-Hydroxysteroid Dehydrogenase-1 (11b-HSD1) in Complex with Piperidyl Benzamide Inhibitor

Structural highlights

3frj is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Gene:	HSD11B1, HSD11, HSD11L (HUMAN)
Activity:	11-beta-hydroxysteroid dehydrogenase, with EC number 1.1.1.146
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[DHI1_HUMAN] Defects in HSD11B1 are a cause of cortisone reductase deficiency (CRD) [MIM:604931]. In CRD, activation of cortisone to cortisol does not occur, resulting in adrenocorticotropin-mediated androgen excess and a phenotype resembling polycystic ovary syndrome (PCOS).

Function

[DHI1_HUMAN] Catalyzes reversibly the conversion of cortisol to the inactive metabolite cortisone. Catalyzes reversibly the conversion of 7-ketocholesterol to 7-beta-hydroxycholesterol. In intact cells, the reaction runs only in one direction, from 7-ketocholesterol to 7-beta-hydroxycholesterol (By similarity).

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

Discovery and optimization of a piperidyl benzamide series of 11beta-HSD1 inhibitors is described. This series was derived from a cyclohexyl benzamide lead structures to address PXR selectivity, high non-specific protein binding, poor solubility, limited in vivo exposure, and in vitro cytotoxicity issues observed with the cyclohexyl benzamide structures. These efforts led to the discovery of piperidyl benzamide 15 which features improved properties over the cyclohexyl benzamide derivatives.

Discovery and optimization of piperidyl benzamide derivatives as a novel class of 11beta-HSD1 inhibitors.,Rew Y, McMinn DL, Wang Z, He X, Hungate RW, Jaen JC, Sudom A, Sun D, Tu H, Ursu S, Villemure E, Walker NP, Yan X, Ye Q, Powers JP Bioorg Med Chem Lett. 2009 Mar 15;19(6):1797-801. Epub 2009 Jan 23. PMID:19217779^[1]

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

References

↑ Rew Y, McMinn DL, Wang Z, He X, Hungate RW, Jaen JC, Sudom A, Sun D, Tu H, Ursu S, Villemure E, Walker NP, Yan X, Ye Q, Powers JP. Discovery and optimization of piperidyl benzamide derivatives as a novel class of 11beta-HSD1 inhibitors. Bioorg Med Chem Lett. 2009 Mar 15;19(6):1797-801. Epub 2009 Jan 23. PMID:19217779 doi:10.1016/j.bmcl.2009.01.058

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3frj"

@@ Line 17: / Line 17: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fr/3frj_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fr/3frj_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 50: / Line 50: @@
 [[Category: Nadp]]
 [[Category: Oxidoreductase]]
+[[Category: Polymorphism]]
 [[Category: Signal-anchor]]
 [[Category: Steroid metabolism]]
 [[Category: Transmembrane]]

3frj

From Proteopedia

Revision as of 07:22, 5 December 2018

Crystal Structure of 11b-Hydroxysteroid Dehydrogenase-1 (11b-HSD1) in Complex with Piperidyl Benzamide Inhibitor

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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