3c3u

Crystal structure of AKR1C1 in complex with NADP and 3,5-dichlorosalicylic acidCrystal structure of AKR1C1 in complex with NADP and 3,5-dichlorosalicylic acid

Structural highlights

3c3u is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.8Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

AK1C1_HUMAN Converts progesterone to its inactive form, 20-alpha-dihydroxyprogesterone (20-alpha-OHP). In the liver and intestine, may have a role in the transport of bile. May have a role in monitoring the intrahepatic bile acid concentration. Has a low bile-binding ability. May play a role in myelin formation.^[1] ^[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 20alpha-hydroxysteroid dehydrogenase (AKR1C1) in ternary complex with the coenzyme NADP (+) and the potent inhibitor 3,5-dichlorosalicylic acid was determined at a resolution of 1.8 A. The inhibitor is held in place by a network of hydrogen bonding interactions with the active site residues Tyr55, His117, and His222. The important role of the nonconserved residues Leu54, His222, Leu306, and Leu308 in inhibitor binding and selectivity was determined by site-directed mutagenesis.

Selectivity determinants of inhibitor binding to human 20alpha-hydroxysteroid dehydrogenase: crystal structure of the enzyme in ternary complex with coenzyme and the potent inhibitor 3,5-dichlorosalicylic acid.,Dhagat U, Endo S, Sumii R, Hara A, El-Kabbani O J Med Chem. 2008 Aug 14;51(15):4844-8. Epub 2008 Jul 12. PMID:18620380^[3]

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

References

↑ Zhang Y, Dufort I, Rheault P, Luu-The V. Characterization of a human 20alpha-hydroxysteroid dehydrogenase. J Mol Endocrinol. 2000 Oct;25(2):221-8. PMID:11013348
↑ 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
↑ Dhagat U, Endo S, Sumii R, Hara A, El-Kabbani O. Selectivity determinants of inhibitor binding to human 20alpha-hydroxysteroid dehydrogenase: crystal structure of the enzyme in ternary complex with coenzyme and the potent inhibitor 3,5-dichlorosalicylic acid. J Med Chem. 2008 Aug 14;51(15):4844-8. Epub 2008 Jul 12. PMID:18620380 doi:10.1021/jm8003575

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OCA

[1] Zhang Y, Dufort I, Rheault P, Luu-The V. Characterization of a human 20alpha-hydroxysteroid dehydrogenase. J Mol Endocrinol. 2000 Oct;25(2):221-8. PMID:11013348

[2] 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

[3] Dhagat U, Endo S, Sumii R, Hara A, El-Kabbani O. Selectivity determinants of inhibitor binding to human 20alpha-hydroxysteroid dehydrogenase: crystal structure of the enzyme in ternary complex with coenzyme and the potent inhibitor 3,5-dichlorosalicylic acid. J Med Chem. 2008 Aug 14;51(15):4844-8. Epub 2008 Jul 12. PMID:18620380 doi:10.1021/jm8003575

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