1mrq

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[[Image:1mrq.gif|left|200px]]
 
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{{Structure
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==Crystal structure of human 20alpha-HSD in ternary complex with NADP and 20alpha-hydroxy-progesterone==
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|PDB= 1mrq |SIZE=350|CAPTION= <scene name='initialview01'>1mrq</scene>, resolution 1.59&Aring;
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<StructureSection load='1mrq' size='340' side='right'caption='[[1mrq]], [[Resolution|resolution]] 1.59&Aring;' scene=''>
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|SITE=
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== Structural highlights ==
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|LIGAND= <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>
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<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>
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|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/20-alpha-hydroxysteroid_dehydrogenase 20-alpha-hydroxysteroid dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.149 1.1.1.149] </span>
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</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>
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|GENE=
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<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>
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|DOMAIN=
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<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>
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|RELATEDENTRY=
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</table>
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1mrq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mrq OCA], [http://www.ebi.ac.uk/pdbsum/1mrq PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1mrq RCSB]</span>
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== Function ==
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}}
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[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>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/mr/1mrq_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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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].
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<div style="clear:both"></div>
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'''Crystal structure of human 20alpha-HSD in ternary complex with NADP and 20alpha-hydroxy-progesterone'''
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==See Also==
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*[[Hydroxysteroid dehydrogenase 3D structures|Hydroxysteroid dehydrogenase 3D structures]]
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== References ==
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==Overview==
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<references/>
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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.
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__TOC__
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</StructureSection>
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==About this Structure==
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1MRQ is a [[Single protein]] structure of 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=1MRQ OCA].
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==Reference==
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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:[http://www.ncbi.nlm.nih.gov/pubmed/12899831 12899831]
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[[Category: 20-alpha-hydroxysteroid dehydrogenase]]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Breton, R.]]
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[[Category: Breton R]]
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[[Category: Cantin, L.]]
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[[Category: Cantin L]]
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[[Category: Couture, J F.]]
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[[Category: Couture JF]]
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[[Category: Labrie, F.]]
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[[Category: Labrie F]]
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[[Category: Legrand, P.]]
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[[Category: Legrand P]]
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[[Category: Luu-The, V.]]
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[[Category: Luu-The V]]
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[[Category: 20alpha-hsd]]
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[[Category: hydroxysteroid dehydrogenase]]
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[[Category: progesterone]]
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[[Category: ternary complex]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:20:14 2008''
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Current revision

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

PDB ID 1mrq

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