1ral

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1ral, resolution 3.Å

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THREE-DIMENSIONAL STRUCTURE OF RAT LIVER 3ALPHA-HYDROXYSTEROID(SLASH)DIHYDRODIOL DEHYDROGENASE: A MEMBER OF THE ALDO-KETO REDUCTASE SUPERFAMILY

Overview

The 3.0-A-resolution x-ray structure of rat liver 3 alpha-hydroxysteroid, dehydrogenase/dihydrodiol dehydrogenase (3 alpha-HSD, EC 1.1.1.50) was, determined by molecular replacement using human placental aldose reductase, as the search model. The protein folds into an alpha/beta or, triose-phosphate isomerase barrel and lacks a canonical Rossmann fold for, binding pyridine nucleotide. The structure contains a concentration of, hydrophobic amino acids that lie in a cavity near the top of the barrel, and that are presumed to be involved in binding hydrophobic substrates, (steroids, prostaglandins, and polycyclic aromatic hydrocarbons) and, inhibitors (nonsteroidal antiinflammatory drugs). At the distal end of, this cavity lie three residues in close proximity that have been, implicated in catalysis by site-directed mutagenesis--Tyr-55, Asp-50, and, Lys-84. Tyr-55 is postulated to act as the general acid. 3 alpha-HSD, shares significant sequence identity with other HSDs that belong to the, aldo-keto reductase superfamily and these may show similar architecture., Other members of this family include prostaglandin F synthase and, rho-crystallin. By contrast, 3 alpha-HSD shares no sequence identity with, HSDs that are members of the short-chain alcohol dehydrogenase family but, does contain the Tyr-Xaa-Xaa-Xaa-Lys consensus sequence implicated in, catalysis in this family. In the 3 alpha-HSD structure these residues are, on the periphery of the barrel and are unlikely to participate in, catalysis.

About this Structure

1RAL is a Single protein structure of sequence from Rattus norvegicus. Active as 3-alpha-hydroxysteroid dehydrogenase (B-specific), with EC number 1.1.1.50 Full crystallographic information is available from OCA.

Reference

Three-dimensional structure of rat liver 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase: a member of the aldo-keto reductase superfamily., Hoog SS, Pawlowski JE, Alzari PM, Penning TM, Lewis M, Proc Natl Acad Sci U S A. 1994 Mar 29;91(7):2517-21. PMID:8146147

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