3d4n

From Proteopedia

(Difference between revisions)

Revision as of 09:40, 14 November 2018

Crystal Structure of Human 11-beta-Hydroxysteroid Dehydrogenase (HSD1) in Complex with Sulfonamide Inhibitor

Structural highlights

3d4n is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	3d3e, 3czr
Gene:	HSD11B1, HSD11, HSD11L (Homo sapiens)
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

We report the discovery of potent benzamide inhibitors of 11beta-hydroxysteroid dehydrogenase (11beta-HSD1). The optimization and correlation of in vitro and in vivo metabolic stability will be described. Through modifications to our initial lead 2, we discovered pyridyl compound 13. This compound has a favorable pharmacokinetic profile across three species and showed a dose-dependent decrease in adipose 11beta-HSD1 activity in a monkey ex vivo pharmacodynamic model.

Discovery of Novel, Potent Benzamide Inhibitors of 11beta-Hydroxysteroid Dehydrogenase Type 1 (11beta-HSD1) Exhibiting Oral Activity in an Enzyme Inhibition ex Vivo Model.,Julian LD, Wang Z, Bostick T, Caille S, Choi R, Degraffenreid M, Di Y, He X, Hungate RW, Jaen JC, Liu J, Monshouwer M, McMinn D, Rew Y, Sudom A, Sun D, Tu H, Ursu S, Walker N, Yan X, Ye Q, Powers JP J Med Chem. 2008 Jun 14;. PMID:18553955^[1]

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

References

↑ Julian LD, Wang Z, Bostick T, Caille S, Choi R, Degraffenreid M, Di Y, He X, Hungate RW, Jaen JC, Liu J, Monshouwer M, McMinn D, Rew Y, Sudom A, Sun D, Tu H, Ursu S, Walker N, Yan X, Ye Q, Powers JP. Discovery of Novel, Potent Benzamide Inhibitors of 11beta-Hydroxysteroid Dehydrogenase Type 1 (11beta-HSD1) Exhibiting Oral Activity in an Enzyme Inhibition ex Vivo Model. J Med Chem. 2008 Jun 14;. PMID:18553955 doi:http://dx.doi.org/10.1021/jm800310g

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/3d4n"

@@ Line 18: / Line 18: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/d4/3d4n_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/d4/3d4n_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 55: / Line 55: @@
 [[Category: Nadp]]
 [[Category: Oxidoreductase]]
+[[Category: Polymorphism]]
 [[Category: Signal-anchor]]
 [[Category: Steroid metabolism]]
 [[Category: Transmembrane]]

3d4n

From Proteopedia

Revision as of 09:40, 14 November 2018

Crystal Structure of Human 11-beta-Hydroxysteroid Dehydrogenase (HSD1) in Complex with Sulfonamide 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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