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==MECHANISM OF INHIBITION OF 3ALPHA,20BETA-HYDROXYSTEROID DEHYDROGENASE BY A LICORICE-DERIVED STEROIDAL INHIBITOR==
==MECHANISM OF INHIBITION OF 3ALPHA,20BETA-HYDROXYSTEROID DEHYDROGENASE BY A LICORICE-DERIVED STEROIDAL INHIBITOR==
<StructureSection load='1hdc' size='340' side='right' caption='[[1hdc]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
<StructureSection load='1hdc' size='340' side='right'caption='[[1hdc]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1hdc]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/"actinomyces_exfoliatus"_waksman_and_curtis_1916 "actinomyces exfoliatus" waksman and curtis 1916]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HDC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1HDC FirstGlance]. <br>
<table><tr><td colspan='2'>[[1hdc]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_exfoliatus Streptomyces exfoliatus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HDC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1HDC FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CBO:CARBENOXOLONE'>CBO</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2&#8491;</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/3-alpha-(or_20-beta)-hydroxysteroid_dehydrogenase 3-alpha-(or 20-beta)-hydroxysteroid dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.53 1.1.1.53] </span></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CBO:CARBENOXOLONE'>CBO</scene></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=1hdc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hdc OCA], [http://pdbe.org/1hdc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1hdc RCSB], [http://www.ebi.ac.uk/pdbsum/1hdc PDBsum]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1hdc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hdc OCA], [https://pdbe.org/1hdc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1hdc RCSB], [https://www.ebi.ac.uk/pdbsum/1hdc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1hdc ProSAT]</span></td></tr>
</table>
</table>
== Function ==
[https://www.uniprot.org/uniprot/HSD_STREX HSD_STREX]
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
Check<jmol>
   <jmolCheckbox>
   <jmolCheckbox>
     <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hd/1hdc_consurf.spt"</scriptWhenChecked>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hd/1hdc_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
   </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=1hdc ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
BACKGROUND: Bacterial 3 alpha, 20 beta-hydroxysteroid dehydrogenase (3 alpha, 20 beta-HSD) reversibly oxidizes the 3 alpha and 20 beta hydroxyl groups of androstanes and pregnanes and uses nicotinamide adenine dinucleotide as a cofactor. 3 alpha, 20 beta-HSD belongs to a family of short-chain dehydrogenases that has a highly conserved Tyr-X-X-X-Lys sequence. The family includes mammalian enzymes involved in hypertension, digestion, fertility and spermatogenesis. Several members of the enzyme family, including 3 alpha, 20 beta-HSD, are competitively inhibited by glycyrrhizic acid, a steroidal compound found in licorice, and its derivative, carbenoxolone, an anti-inflammatory glucocorticoid. RESULTS: The three-dimensional structure of the enzyme-carbenoxolone complex has been determined and refined at 2.2 A resolution to a crystallographic R-factor of 19.4%. The hemisuccinate side chain of carbenoxolone makes a hydrogen bond with the hydroxyl group of the conserved residue Tyr152 and occupies the position of the nicotinamide ring of the cofactor. The occupancies of the inhibitor in four independent catalytic sites refine to 100%, 95%, 54% and 36%. CONCLUSIONS: The steroid binds at the catalytic site in a mode much like the previously proposed mode of binding of the substrate cortisone. No bound cofactor molecules were found. The varying occupancy of steroid molecules observed in the four catalytic sites is either due to packing differences or indicates a cooperative effect among the four sites. The observed binding accounts for the inhibition of 3 alpha, 20 beta-HSD.
Mechanism of inhibition of 3 alpha, 20 beta-hydroxysteroid dehydrogenase by a licorice-derived steroidal inhibitor.,Ghosh D, Erman M, Wawrzak Z, Duax WL, Pangborn W Structure. 1994 Oct 15;2(10):973-80. PMID:7866748<ref>PMID:7866748</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1hdc" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Hydroxysteroid dehydrogenase|Hydroxysteroid dehydrogenase]]
*[[Hydroxysteroid dehydrogenase 3D structures|Hydroxysteroid dehydrogenase 3D structures]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Actinomyces exfoliatus waksman and curtis 1916]]
[[Category: Large Structures]]
[[Category: Ghosh, D]]
[[Category: Streptomyces exfoliatus]]
[[Category: Oxidoreductase]]
[[Category: Ghosh D]]

Latest revision as of 10:27, 7 February 2024

MECHANISM OF INHIBITION OF 3ALPHA,20BETA-HYDROXYSTEROID DEHYDROGENASE BY A LICORICE-DERIVED STEROIDAL INHIBITORMECHANISM OF INHIBITION OF 3ALPHA,20BETA-HYDROXYSTEROID DEHYDROGENASE BY A LICORICE-DERIVED STEROIDAL INHIBITOR

Structural highlights

1hdc is a 4 chain structure with sequence from Streptomyces exfoliatus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.2Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

HSD_STREX

Evolutionary Conservation

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

See Also

1hdc, resolution 2.20Å

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