2ipf: Difference between revisions

← Older edit

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-{{Seed}}
-[[Image:2ipf.png|left|200px]]
-<!--
+==Crystal structure of 17alpha-hydroxysteroid dehydrogenase in complex with NADP+ and epi-testosterone==
-The line below this paragraph, containing "STRUCTURE_2ipf", creates the "Structure Box" on the page.
+<StructureSection load='2ipf' size='340' side='right'caption='[[2ipf]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[2ipf]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2IPF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2IPF FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.85&#8491;</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=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FFA:(10ALPHA,13ALPHA,14BETA,17ALPHA)-17-HYDROXYANDROST-4-EN-3-ONE'>FFA</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene></td></tr>
-{{STRUCTURE_2ipf|  PDB=2ipf  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2ipf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ipf OCA], [https://pdbe.org/2ipf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ipf RCSB], [https://www.ebi.ac.uk/pdbsum/2ipf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ipf ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/AK1CL_MOUSE AK1CL_MOUSE] NADP-dependent 17-alpha-hydroxysteroid dehydrogenase that converts 5-alpha-androstane-3,17-dione into androsterone. Has lower 3-alpha-hydroxysteroid dehydrogenase activity. Has broad substrate specificity and acts on various 17-alpha-hydroxysteroids, 17-ketosteroids, 3-alpha hydroxysteroids and 3-ketosteroids. Reduction of keto groups is strictly stereoselective. Reduction of 17-ketosteroids yields only 17-alpha-hydroxysteroids. Likewise, reduction of 3-ketosteroids yields only 3-alpha-hydroxysteroids.<ref>PMID:15577209</ref> <ref>PMID:16018803</ref> <ref>PMID:17034817</ref>
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ip/2ipf_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </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/main_output.php?pdb_ID=2ipf ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The mouse 17alpha-hydroxysteroid dehydrogenase (m17alpha-HSD) is the unique known member of the aldo-keto reductase (AKR) superfamily able to catalyze efficiently and in a stereospecific manner the conversion of androstenedione (Delta4) into epi-testosterone (epi-T), the 17alpha-epimer of testosterone. Structural and mutagenic studies had already identified one of the residues delineating the steroid-binding cavity, A24, as the major molecular determinant for the stereospecificity of m17alpha-HSD. We report here a ternary complex crystal structure (m17alpha-HSD:NADP(+):epi-T) determined at 1.85 A resolution that confirms this and reveals a unique steroid-binding mode for an AKR enzyme. Indeed, in addition to the interactions found in all other AKRs (van der Waals contacts stabilizing the core of the steroid and the hydrogen bonds established at the catalytic site by the Y55 and H117 residues with the oxygen atom of the ketone group to be reduced), m17alpha-HSD establishes with the other extremity of the steroid nucleus an additional interaction involving K31. By combining direct mutagenesis and kinetic studies, we found that the elimination of this hydrogen bond did not affect the affinity of the enzyme for its steroid substrate but led to a slight but significant increase of its catalytic efficiency (k(cat)/K(m)), suggesting a role for K31 in the release of the steroidal product at the end of the reaction. This previously unobserved steroid-binding mode for an AKR is similar to that adopted by other steroid-binding proteins, the hydroxysteroid dehydrogenases of the short-chain dehydrogenases/reductases (SDR) family and the steroid hormone nuclear receptors. Mutagenesis and structural studies made on the human type 3 3alpha-HSD, a closely related enzyme that shares 73% amino acids identity with the m17alpha-HSD, also revealed that the residue at position 24 of these two enzymes directly affects the binding and/or the release of NADPH, in addition to its role in their 17alpha/17beta stereospecificity.
-===Crystal structure of 17alpha-hydroxysteroid dehydrogenase in complex with NADP+ and epi-testosterone===
+Mouse 17alpha-hydroxysteroid dehydrogenase (AKR1C21) binds steroids differently from other aldo-keto reductases: identification and characterization of amino acid residues critical for substrate binding.,Faucher F, Cantin L, Pereira de Jesus-Tran K, Lemieux M, Luu-The V, Labrie F, Breton R J Mol Biol. 2007 Jun 1;369(2):525-40. Epub 2007 Mar 27. PMID:17442338<ref>PMID:17442338</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 2ipf" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_17442338}}, adds the Publication Abstract to the page
+*[[Hydroxysteroid dehydrogenase 3D structures|Hydroxysteroid dehydrogenase 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 17442338 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_17442338}}
+__TOC__
+</StructureSection>
-==About this Structure==
+[[Category: Large Structures]]
-IPF is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2IPF OCA].
-==Reference==
-Mouse 17alpha-hydroxysteroid dehydrogenase (AKR1C21) binds steroids differently from other aldo-keto reductases: identification and characterization of amino acid residues critical for substrate binding., Faucher F, Cantin L, Pereira de Jesus-Tran K, Lemieux M, Luu-The V, Labrie F, Breton R, J Mol Biol. 2007 Jun 1;369(2):525-40. Epub 2007 Mar 27. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17442338 17442338]
 [[Category: Mus musculus]]
-[[Category: Single protein]]
+[[Category: Breton R]]
-[[Category: Breton, R.]]
+[[Category: Cantin L]]
-[[Category: Cantin, L.]]
+[[Category: Faucher F]]
-[[Category: Faucher, F.]]
+[[Category: Labrie F]]
-[[Category: Jesus-Tran, K Pereira de.]]
+[[Category: Luu-the V]]
-[[Category: Labrie, F.]]
+[[Category: Pereira de Jesus-Tran K]]
-[[Category: Luu-the, V.]]
-[[Category: 17a-hsd]]
-[[Category: Akr]]
-[[Category: Akr1c21]]
-[[Category: Aldo-keto reductase]]
-[[Category: Epi-testosterone]]
-[[Category: Hsd]]
-[[Category: Hydroxysteroid dehydrogenase]]
-[[Category: Open conformation]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 16:01:54 2008''