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1j96

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Revision as of 14:21, 10 September 2015

Human 3alpha-HSD type 3 in Ternary Complex with NADP and Testosterone

Structural highlights

1j96 is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Activity:	3-alpha-hydroxysteroid dehydrogenase (Re-specific), with EC number 1.1.1.213
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

Disease

[AK1C2_HUMAN] Defects in AKR1C2 are a cause of 46,XY sex reversal type 8 (SRXY8) [MIM:614279]. A disorder of sex development. Affected individuals have a 46,XY karyotype but present as phenotypically normal females.^[1]

Function

[AK1C2_HUMAN] Works in concert with the 5-alpha/5-beta-steroid reductases to convert steroid hormones into the 3-alpha/5-alpha and 3-alpha/5-beta-tetrahydrosteroids. Catalyzes the inactivation of the most potent androgen 5-alpha-dihydrotestosterone (5-alpha-DHT) to 5-alpha-androstane-3-alpha,17-beta-diol (3-alpha-diol). Has a high bile-binding ability.^[2]

Evolutionary Conservation

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

Publication Abstract from PubMed

The first crystallographic structure of human type 3 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD3, AKR1C2), an enzyme playing a critical role in steroid hormone metabolism, has been determined in complex with testosterone and NADP at 1.25-A resolution. The enzyme's 17beta-HSD activity was studied in comparison with its 3alpha-HSD activity. The enzyme catalyzes the inactivation of dihydrotestosterone into 5alpha-androstane-3alpha,17beta-diol (3alpha-diol) as well as the transformation of androstenedione into testosterone. Using our homogeneous and highly active enzyme preparation, we have obtained 150-fold higher 3alpha-HSD specificity as compared with the former reports in the literature. Although the rat and the human 3alpha-HSDs share 81% sequence homology, our structure reveals significantly different geometries of the active sites. Substitution of the Ser(222) by a histidine in the human enzyme may compel the steroid to adopt a different binding to that previously described for the rat (Bennett, M. J., Albert, R. H., Jez, J. M., Ma, H., Penning, T. M., and Lewis, M. (1997) Structure 5, 799-T812). Furthermore, we showed that the affinity for the cofactor is higher in the human 3alpha-HSD3 than the rat enzyme due to the presence of additional hydrogen bonds on the adenine moiety and that the cofactor is present under its reduced form in the active site in our preparation.

Structure of the human 3alpha-hydroxysteroid dehydrogenase type 3 in complex with testosterone and NADP at 1.25-A resolution.,Nahoum V, Gangloff A, Legrand P, Zhu DW, Cantin L, Zhorov BS, Luu-The V, Labrie F, Breton R, Lin SX J Biol Chem. 2001 Nov 9;276(45):42091-8. Epub 2001 Aug 20. PMID:11514561^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Fluck CE, Meyer-Boni M, Pandey AV, Kempna P, Miller WL, Schoenle EJ, Biason-Lauber A. Why boys will be boys: two pathways of fetal testicular androgen biosynthesis are needed for male sexual differentiation. Am J Hum Genet. 2011 Aug 12;89(2):201-18. doi: 10.1016/j.ajhg.2011.06.009. Epub, 2011 Jul 28. PMID:21802064 doi:10.1016/j.ajhg.2011.06.009
↑ Hara A, Matsuura K, Tamada Y, Sato K, Miyabe Y, Deyashiki Y, Ishida N. Relationship of human liver dihydrodiol dehydrogenases to hepatic bile-acid-binding protein and an oxidoreductase of human colon cells. Biochem J. 1996 Jan 15;313 ( Pt 2):373-6. PMID:8573067
↑ Nahoum V, Gangloff A, Legrand P, Zhu DW, Cantin L, Zhorov BS, Luu-The V, Labrie F, Breton R, Lin SX. Structure of the human 3alpha-hydroxysteroid dehydrogenase type 3 in complex with testosterone and NADP at 1.25-A resolution. J Biol Chem. 2001 Nov 9;276(45):42091-8. Epub 2001 Aug 20. PMID:11514561 doi:10.1074/jbc.M105610200

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 See Also
7 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1j96"

@@ Line 2: / Line 2: @@
 <StructureSection load='1j96' size='340' side='right' caption='[[1j96]], [[Resolution|resolution]] 1.25&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1j96]] is a 2 chain structure with 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=1J96 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1J96 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1j96]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1J96 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1J96 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=TES:TESTOSTERONE'>TES</scene></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-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] </span></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-hydroxysteroid_dehydrogenase_(Re-specific) 3-alpha-hydroxysteroid dehydrogenase (Re-specific)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.213 1.1.1.213] </span></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=1j96 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1j96 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1j96 RCSB], [http://www.ebi.ac.uk/pdbsum/1j96 PDBsum]</span></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=1j96 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1j96 OCA], [http://pdbe.org/1j96 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1j96 RCSB], [http://www.ebi.ac.uk/pdbsum/1j96 PDBsum]</span></td></tr>
 </table>
 == Disease ==
@@ Line 29: / Line 29: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 1j96" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 36: / Line 37: @@
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Labrie, F]]
 [[Category: Lin, S X]]

1j96

From Proteopedia

Revision as of 14:21, 10 September 2015

Human 3alpha-HSD type 3 in Ternary Complex with NADP and Testosterone

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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