Crystal Structure of Human Liver ∆-3-ketosteroid 5β-reductase (akr1d1) and Implications for Substrate Binding and Catalysis*
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چکیده
CRYSTAL STRUCTURE OF HUMAN LIVER ∆-3-KETOSTEROID 5β-REDUCTASE (AKR1D1) AND IMPLICATIONS FOR SUBSTRATE BINDING AND CATALYSIS* Luigi Di Costanzo, Jason E. Drury, Trevor M. Penning, and David W. Christianson From the Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6323, and Center of Excellence in Environmental Toxicology and Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6084 Running title: crystal structure of ∆-3-Ketosteroid 5β-reductase (AKR1D1) Address correspondence to: Dr. David W. Christianson, Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6323; Tel: 215-898-5714; Fax: 215-573-2201; E-mail: [email protected]; and Dr. Trevor M. Penning, Department of Pharmacology, University of Pennsylvania, 130C John Morgan Bldg., 3620 Hamilton Walk, Philadelphia, PA, 19104-6084. Phone: 215-898-9445; Fax: 215-573-2236; E-mail: [email protected]
منابع مشابه
Stereospecific reduction of 5β-reduced steroids by human ketosteroid reductases of the AKR (aldo-keto reductase) superfamily: role of AKR1C1-AKR1C4 in the metabolism of testosterone and progesterone via the 5β-reductase pathway.
Active sex hormones such as testosterone and progesterone are metabolized to tetrahydrosteroids in the liver to terminate hormone action. One main metabolic pathway, the 5β-pathway, involves 5β-steroid reductase (AKR1D1, where AKR refers to the aldo-keto reductase superfamily), which catalyses the reduction of the 4-ene structure, and ketosteroid reductases (AKR1C1-AKR1C4), which catalyse the s...
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