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3klm

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Revision as of 07:02, 7 October 2020

17beta-HSD1 in complex with DHT

Structural highlights

3klm is a 1 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:	,
Activity:	17-beta-estradiol 17-dehydrogenase, with EC number 1.1.1.62
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[DHB1_HUMAN] Favors the reduction of estrogens and androgens. Also has 20-alpha-HSD activity. Uses preferentially NADH.

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

The active estrogen estradiol (E2) stimulates breast cancer cell (BCC) growth, whereas the androgen dihydrotestosterone (DHT) has shown an antiproliferative effect. The principal product synthesized by the 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1) is E2, although we have demonstrated that the purified enzyme also inactivates DHT. However, the direct roles of 17beta-HSD1 in sex-hormone regulation and BCC proliferation have not been completely established. Here, we show that 17beta-HSD1 inhibition suppresses DHT catabolism by 19%, whereas knockdown of the gene expression increases the concentration of DHT by 41% in the T47D BCC line. The 17beta-HSD1/DHT complex crystal structure reveals that DHT binds in both normal and reverse modes, but the latter mode leading to O3 reduction is preferred with stronger interactions. Using RNA interference and an inhibitor of 17beta-HSD1, we demonstrate that 17beta-HSD1 expression is negatively correlated to DHT levels in BCC but positively correlated to estrone reduction, E2 levels, and cell proliferation. 17beta-HSD1 inhibition reduces DHT inactivation, increasing the antiproliferative effect by DHT in T47D cells after 8 d treatment. Thus, 17beta-HSD1 up-regulates BCC growth by a dual action on estradiol synthesis and DHT inactivation. We have further demonstrated that 17beta-HSD1 can enhance the E2-induced expression of the endogenous estrogen-responsive gene pS2, providing an important information regarding the modulation of the estrogen responsiveness by 17beta-HSD1 that may also contribute to BCC growth. These results strongly support the rationale for inhibiting 17beta-HSD1 in breast cancer therapy to eliminate estrogen activation via the sulfatase pathway while avoiding the deprivation of DHT.

17beta-hydroxysteroid dehydrogenase type 1 stimulates breast cancer by dihydrotestosterone inactivation in addition to estradiol production.,Aka JA, Mazumdar M, Chen CQ, Poirier D, Lin SX Mol Endocrinol. 2010 Apr;24(4):832-45. Epub 2010 Feb 19. PMID:20172961^[1]

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

References

↑ Aka JA, Mazumdar M, Chen CQ, Poirier D, Lin SX. 17beta-hydroxysteroid dehydrogenase type 1 stimulates breast cancer by dihydrotestosterone inactivation in addition to estradiol production. Mol Endocrinol. 2010 Apr;24(4):832-45. Epub 2010 Feb 19. PMID:20172961 doi:10.1210/me.2009-0468

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/3klm"

@@ Line 1: / Line 1: @@
 ==17beta-HSD1 in complex with DHT==
-<StructureSection load='3klm' size='340' side='right' caption='[[3klm]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
+<StructureSection load='3klm' size='340' side='right'caption='[[3klm]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3klm]] is a 1 chain structure with 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=3KLM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3KLM FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3klm]] is a 1 chain structure with 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=3KLM OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=3KLM FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DHT:5-ALPHA-DIHYDROTESTOSTERONE'>DHT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DHT:5-ALPHA-DIHYDROTESTOSTERONE'>DHT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/17-beta-estradiol_17-dehydrogenase 17-beta-estradiol 17-dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.62 1.1.1.62] </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=3klm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3klm OCA], [http://pdbe.org/3klm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3klm RCSB], [http://www.ebi.ac.uk/pdbsum/3klm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3klm ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=3klm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3klm OCA], [http://pdbe.org/3klm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3klm RCSB], [http://www.ebi.ac.uk/pdbsum/3klm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3klm ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 31: / Line 31: @@
 ==See Also==
-*[[Hydroxysteroid dehydrogenase|Hydroxysteroid dehydrogenase]]
+*[[Hydroxysteroid dehydrogenase 3D structures|Hydroxysteroid dehydrogenase 3D structures]]
 == References ==
 <references/>
@@ Line 38: / Line 38: @@
 [[Category: 17-beta-estradiol 17-dehydrogenase]]
 [[Category: Homo sapiens]]
+[[Category: Large Structures]]
 [[Category: Mazumdar, M]]
 [[Category: Dht]]

3klm

From Proteopedia

Revision as of 07:02, 7 October 2020

17beta-HSD1 in complex with DHT

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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