3caq

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Template:STRUCTURE 3caq

Contents 1 Crystal structure of 5beta-reductase (AKR1D1) in complex with NADPH 2 Disease 3 Function 4 About this Structure 5 Reference

Crystal structure of 5beta-reductase (AKR1D1) in complex with NADPH

Template:ABSTRACT PUBMED 19075558

Disease

[AK1D1_HUMAN] Defects in AKR1D1 are the cause of congenital bile acid synthesis defect type 2 (CBAS2) [MIM:235555]; also known as cholestasis with delta(4)-3-oxosteroid 5-beta-reductase deficiency. Patients with this liver disease show absence or low levels of chenodeoxycholic acid and cholic acid in plasma and urine.^[1][2]

Function

[AK1D1_HUMAN] Efficiently catalyzes the reduction of progesterone, androstenedione, 17-alpha-hydroxyprogesterone and testosterone to 5-beta-reduced metabolites. The bile acid intermediates 7-alpha,12-alpha-dihydroxy-4-cholesten-3-one and 7-alpha-hydroxy-4-cholesten-3-one can also act as substrates.

About this Structure

3caq is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

• Faucher F, Cantin L, Luu-The V, Labrie F, Breton R. Crystal structures of human Delta4-3-ketosteroid 5beta-reductase (AKR1D1) reveal the presence of an alternative binding site responsible for substrate inhibition. Biochemistry. 2008 Dec 23;47(51):13537-46. PMID:19075558 doi:10.1021/bi801276h

1. ↑ Lemonde HA, Custard EJ, Bouquet J, Duran M, Overmars H, Scambler PJ, Clayton PT. Mutations in SRD5B1 (AKR1D1), the gene encoding delta(4)-3-oxosteroid 5beta-reductase, in hepatitis and liver failure in infancy. Gut. 2003 Oct;52(10):1494-9. PMID:12970144
2. ↑ Gonzales E, Cresteil D, Baussan C, Dabadie A, Gerhardt MF, Jacquemin E. SRD5B1 (AKR1D1) gene analysis in delta(4)-3-oxosteroid 5beta-reductase deficiency: evidence for primary genetic defect. J Hepatol. 2004 Apr;40(4):716-8. PMID:15030995 doi:10.1016/j.jhep.2003.12.024