From Proteopedia
(Difference between revisions)
proteopedia linkproteopedia link
|
|
| Line 1: |
Line 1: |
| - | [[Image:1ihi.jpg|left|200px]] | + | {{Seed}} |
| | + | [[Image:1ihi.png|left|200px]] |
| | | | |
| | <!-- | | <!-- |
| Line 9: |
Line 10: |
| | {{STRUCTURE_1ihi| PDB=1ihi | SCENE= }} | | {{STRUCTURE_1ihi| PDB=1ihi | SCENE= }} |
| | | | |
| - | '''Crystal Structure of Human Type III 3-alpha-Hydroxysteroid Dehydrogenase/Bile Acid Binding Protein (AKR1C2) Complexed with NADP+ and Ursodeoxycholate'''
| + | ===Crystal Structure of Human Type III 3-alpha-Hydroxysteroid Dehydrogenase/Bile Acid Binding Protein (AKR1C2) Complexed with NADP+ and Ursodeoxycholate=== |
| | | | |
| | | | |
| - | ==Overview==
| + | <!-- |
| - | 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. | + | The line below this paragraph, {{ABSTRACT_PUBMED_11513593}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 11513593 is the PubMed ID number. |
| | + | --> |
| | + | {{ABSTRACT_PUBMED_11513593}} |
| | | | |
| | ==About this Structure== | | ==About this Structure== |
| Line 32: |
Line 36: |
| | [[Category: Protein-nadp-bile acid complex]] | | [[Category: Protein-nadp-bile acid complex]] |
| | [[Category: Ternary complex]] | | [[Category: Ternary complex]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 20:00:20 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 12:11:52 2008'' |
Revision as of 09:11, 1 July 2008
Template:STRUCTURE 1ihi
Crystal Structure of Human Type III 3-alpha-Hydroxysteroid Dehydrogenase/Bile Acid Binding Protein (AKR1C2) Complexed with NADP+ and Ursodeoxycholate
Template:ABSTRACT PUBMED 11513593
About this Structure
1IHI is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Tue Jul 1 12:11:52 2008
