1mrq: Difference between revisions

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<StructureSection load='1mrq' size='340' side='right'caption='[[1mrq]], [[Resolution|resolution]] 1.59&Aring;' scene=''>
<StructureSection load='1mrq' size='340' side='right'caption='[[1mrq]], [[Resolution|resolution]] 1.59&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1mrq]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MRQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1MRQ FirstGlance]. <br>
<table><tr><td colspan='2'>[[1mrq]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MRQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1MRQ FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=STR:PROGESTERONE'>STR</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]] 1.59&#8491;</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/20-alpha-hydroxysteroid_dehydrogenase 20-alpha-hydroxysteroid dehydrogenase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.149 1.1.1.149] </span></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=STR:PROGESTERONE'>STR</scene></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=1mrq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mrq OCA], [https://pdbe.org/1mrq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1mrq RCSB], [https://www.ebi.ac.uk/pdbsum/1mrq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1mrq ProSAT]</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=1mrq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mrq OCA], [https://pdbe.org/1mrq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1mrq RCSB], [https://www.ebi.ac.uk/pdbsum/1mrq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1mrq ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[https://www.uniprot.org/uniprot/AK1C1_HUMAN AK1C1_HUMAN]] Converts progesterone to its inactive form, 20-alpha-dihydroxyprogesterone (20-alpha-OHP). In the liver and intestine, may have a role in the transport of bile. May have a role in monitoring the intrahepatic bile acid concentration. Has a low bile-binding ability. May play a role in myelin formation.<ref>PMID:11013348</ref> <ref>PMID:8573067</ref>
[https://www.uniprot.org/uniprot/AK1C1_HUMAN AK1C1_HUMAN] Converts progesterone to its inactive form, 20-alpha-dihydroxyprogesterone (20-alpha-OHP). In the liver and intestine, may have a role in the transport of bile. May have a role in monitoring the intrahepatic bile acid concentration. Has a low bile-binding ability. May play a role in myelin formation.<ref>PMID:11013348</ref> <ref>PMID:8573067</ref>  
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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</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=1mrq 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=1mrq ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Human 20alpha-hydroxysteroid dehydrogenase (h20alpha-HSD; AKR1C1) catalyzes the transformation of progesterone (Prog) into 20alpha-hydroxy-progesterone (20alpha-OHProg). Although h20alpha-HSD shares 98% sequence identity with human type 3 3alpha-HSD (h3alpha-HSD3, AKR1C2), these two enzymes differ greatly in their activities. In order to explain these differences, we have solved the crystal structure of h20alpha-HSD in a ternary complex with NADP(+) and 20alpha-OHProg at 1.59A resolution. The steroid is stabilized by numerous hydrophobic interactions and a hydrogen bond between its O20 and the N(epsilon ) atom of His222. This new interaction prevents the formation of a hydrogen bond with the cofactor, as seen in h3alpha-HSD3 ternary complexes. By combining structural, direct mutagenesis and kinetic studies, we found that the H(222)I substitution decreases the K(m) value for the cofactor 95-fold. With these results, we hypothesize that the rotation of the lateral chain of His222 could be a mediating step between the transformation of Prog and the release of the cofactor. Moreover, crystal structure analysis and direct mutagenesis experiments lead us to identify a new residue involved in the binding of Prog. Indeed, the R(304)L substitution leads to a 65-fold decrease in the K(m) value for Prog reduction. We thus propose that Prog is maintained in a new steroid-binding site composed mainly of residues found in the carboxy-terminal region of the protein.
Human 20alpha-hydroxysteroid dehydrogenase: crystallographic and site-directed mutagenesis studies lead to the identification of an alternative binding site for C21-steroids.,Couture JF, Legrand P, Cantin L, Luu-The V, Labrie F, Breton R J Mol Biol. 2003 Aug 15;331(3):593-604. PMID:12899831<ref>PMID:12899831</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1mrq" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: 20-alpha-hydroxysteroid dehydrogenase]]
[[Category: Homo sapiens]]
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Breton, R]]
[[Category: Breton R]]
[[Category: Cantin, L]]
[[Category: Cantin L]]
[[Category: Couture, J F]]
[[Category: Couture JF]]
[[Category: Labrie, F]]
[[Category: Labrie F]]
[[Category: Legrand, P]]
[[Category: Legrand P]]
[[Category: Luu-The, V]]
[[Category: Luu-The V]]
[[Category: 20alpha-hsd]]
[[Category: Hydroxysteroid dehydrogenase]]
[[Category: Oxidoreductase]]
[[Category: Progesterone]]
[[Category: Ternary complex]]

Latest revision as of 07:47, 14 February 2024

Crystal structure of human 20alpha-HSD in ternary complex with NADP and 20alpha-hydroxy-progesterone

1mrq, resolution 1.59Å

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