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New page: left|200px<br /><applet load="1lwi" size="450" color="white" frame="true" align="right" spinBox="true" caption="1lwi, resolution 2.7Å" /> '''3-ALPHA-HYDROXYSTEROI...
 
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[[Image:1lwi.jpg|left|200px]]<br /><applet load="1lwi" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1lwi, resolution 2.7&Aring;" />
'''3-ALPHA-HYDROXYSTEROID/DIHYDRODIOL DEHYDROGENASE FROM RATTUS NORVEGICUS'''<br />


==Overview==
==3-ALPHA-HYDROXYSTEROID/DIHYDRODIOL DEHYDROGENASE FROM RATTUS NORVEGICUS==
Rat liver 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase (3 alpha-HSD), inactivates circulating steroid hormones and is involved in polycyclic, aromatic hydrocarbon (PAH) carcinogenesis. It is the only HSD of known, structure in the aldo-keto reductase (AKR) superfamily and may provide a, paradigm for other mammalian HSDs in this family. The structure of the 3, alpha-HSD.NADP+ binary complex has been determined at 2.7 A resolution and, refined to a crystallographic R-factor of 23.4% with good geometry. The, model is similar to other binary complexes in the AKR superfamily in that, NADP+ binds at the C-terminal end of an alpha/beta barrel. However, it is, unique in that NADP+ is bound in two alternate conformations, probably, because of the lack of a salt-linked "safety belt" over the pyrophosphate, bridge. The structure supports a previously proposed catalytic mechanism, for carbonyl reduction in which Tyr 55 is the general acid, and its, effective pKa is lowered by the adjacent Lys 84. We present evidence that, the structurally distinct short-chain dehydrogenase/reductase (SDR), superfamily may have convergently evolved a similar catalytic mechanism., Insight into substrate binding is offered by a crystal packing contact in, which a neighboring molecule inserts a tryptophan residue (Trp 227) into, an apolar cleft in 3 alpha-HSD. This cleft is proximal to the bound NADP+, cofactor and contains a surface of apolar residues (Leu 54, Trp 86, Leu, 122, Phe 128, Phe 129, Leu 137, Phe 139), making it a likely candidate for, the substrate-binding site. Thus, in forming this crystal contact, Trp 227, may mimic a portion of a bound steroid. In addition, we propose that a, water molecule in the active site indicates the position of the hydroxyl, oxygen in a 3 alpha-hydroxysteroid substrate. Knowledge of the position of, this water molecule, combined with the stereochemistry of hydride, transfer, suggests that the alpha face of a bound steroid will be oriented, toward the side of the apolar cleft containing Trp 86.
<StructureSection load='1lwi' size='340' side='right'caption='[[1lwi]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1lwi]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LWI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1LWI FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</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=1lwi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lwi OCA], [https://pdbe.org/1lwi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1lwi RCSB], [https://www.ebi.ac.uk/pdbsum/1lwi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1lwi ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/DIDH_RAT DIDH_RAT] Besides being a 3-alpha-hydroxysteroid dehydrogenase, the enzyme can accomplish diverse functions: as quinone reductase, as an aromatic alcohol dehydrogenase, as dihydrodiol dehydrogenase, and as 9-, 11-, and 15-hydroxyprostaglandin dehydrogenase.
== 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/lw/1lwi_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=1lwi ConSurf].
<div style="clear:both"></div>


==About this Structure==
==See Also==
1LWI is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with NAP as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/3-alpha-hydroxysteroid_dehydrogenase_(A-specific) 3-alpha-hydroxysteroid dehydrogenase (A-specific)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.213 1.1.1.213] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1LWI OCA].
*[[Hydroxysteroid dehydrogenase|Hydroxysteroid dehydrogenase]]
 
*[[Hydroxysteroid dehydrogenase 3D structures|Hydroxysteroid dehydrogenase 3D structures]]
==Reference==
__TOC__
Structure of 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase complexed with NADP+., Bennett MJ, Schlegel BP, Jez JM, Penning TM, Lewis M, Biochemistry. 1996 Aug 20;35(33):10702-11. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=8718859 8718859]
</StructureSection>
[[Category: 3-alpha-hydroxysteroid dehydrogenase (A-specific)]]
[[Category: Large Structures]]
[[Category: Rattus norvegicus]]
[[Category: Rattus norvegicus]]
[[Category: Single protein]]
[[Category: Bennett MJ]]
[[Category: Bennett, M.J.]]
[[Category: Jez JM]]
[[Category: Jez, J.M.]]
[[Category: Lewis M]]
[[Category: Lewis, M.]]
[[Category: Penning TM]]
[[Category: Penning, T.M.]]
[[Category: Schlegel BP]]
[[Category: Schlegel, B.P.]]
[[Category: NAP]]
[[Category: nad]]
[[Category: oxidoreductase]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 20:56:23 2007''
Retrieved from "https://proteopedia.org/1lwi"