1ihi

From Proteopedia

(Difference between revisions)

Revision as of 10:31, 30 October 2019

Crystal Structure of Human Type III 3-alpha-Hydroxysteroid Dehydrogenase/Bile Acid Binding Protein (AKR1C2) Complexed with NADP+ and Ursodeoxycholate

Structural highlights

1ihi 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-hydroxycholanate dehydrogenase, with EC number 1.1.1.52
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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 crystal structure of human type III 3alpha-hydroxysteroid dehydrogenase (HSD)/bile acid binding protein (AKR1C2) complexed with NADP(+) and 3alpha,7beta-dihydroxy-5beta-cholanic acid (ursodeoxycholate) at 3.0 A resolution is presented. Thus, the three-dimensional structure has now been solved for a human HSD member of the aldo-keto reductase superfamily. AKR1C2 is implicated in the prostatic production of the potent androgen 5alpha-dihydrotestosterone and the hepatic transport of bile acids. It also catalyzes the formation of the neurosteroid 3alpha-hydroxy-5alpha-pregnan-20-one in the central nervous system, and its allosteric modulation by fluoxetine has been linked to the use of this drug for premenstrual dsyphoria. Like other members of the superfamily, AKR1C2 folds into an alpha/beta-barrel and binds NADP(+) in an extended conformation. The carboxylate of ursodeoxycholate binds to AKR1C2 in the oxyanion hole at the active site. More interestingly, the orientation of ursodeoxycholate is essentially "backwards" and "upside-down" from that observed for testosterone in the related rat 3alpha-HSD.NADP(+).testosterone ternary complex, where testosterone assumes the position of a 3-ketosteroid substrate. The orientation of ursodeoxycholate is thus similar to that expected of a 17beta-HSD substrate. The ternary structure explains the ability of AKR1C2 to catalyze 3alpha-, 17beta-, and 20alpha-HSD reactions. Comparison of the steroid binding pocket of AKR1C2 with that of rat 3alpha-HSD reveals significant differences in the positions of conserved and nonconserved loop residues, providing insights into the structural basis for the functional flexibility that is observed in all the human 3alpha-HSD isoforms but not in the rat isoform.

Crystal structure of human type III 3alpha-hydroxysteroid dehydrogenase/bile acid binding protein complexed with NADP(+) and ursodeoxycholate.,Jin Y, Stayrook SE, Albert RH, Palackal NT, Penning TM, Lewis M Biochemistry. 2001 Aug 28;40(34):10161-8. PMID:11513593^[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
↑ Jin Y, Stayrook SE, Albert RH, Palackal NT, Penning TM, Lewis M. Crystal structure of human type III 3alpha-hydroxysteroid dehydrogenase/bile acid binding protein complexed with NADP(+) and ursodeoxycholate. Biochemistry. 2001 Aug 28;40(34):10161-8. PMID:11513593

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/1ihi"

@@ Line 1: / Line 1: @@
 ==Crystal Structure of Human Type III 3-alpha-Hydroxysteroid Dehydrogenase/Bile Acid Binding Protein (AKR1C2) Complexed with NADP+ and Ursodeoxycholate==
-<StructureSection load='1ihi' size='340' side='right' caption='[[1ihi]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
+<StructureSection load='1ihi' size='340' side='right'caption='[[1ihi]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[1ihi]] 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=1IHI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1IHI FirstGlance]. <br>
@@ Line 31: / Line 31: @@
 </div>
 <div class="pdbe-citations 1ihi" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Hydroxysteroid dehydrogenase 3D structures|Hydroxysteroid dehydrogenase 3D structures]]
 == References ==
 <references/>
@@ Line 37: / Line 40: @@
 [[Category: 3-alpha-hydroxycholanate dehydrogenase]]
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Albert, R H]]
 [[Category: Jin, Y]]

1ihi

From Proteopedia

Revision as of 10:31, 30 October 2019

Crystal Structure of Human Type III 3-alpha-Hydroxysteroid Dehydrogenase/Bile Acid Binding Protein (AKR1C2) Complexed with NADP+ and Ursodeoxycholate

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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