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PDBsum entry 1ral
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Oxidoreductase
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PDB id
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1ral
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References listed in PDB file
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Key reference
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Title
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Three-Dimensional structure of rat liver 3 alpha-Hydroxysteroid/dihydrodiol dehydrogenase: a member of the aldo-Keto reductase superfamily.
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Authors
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S.S.Hoog,
J.E.Pawlowski,
P.M.Alzari,
T.M.Penning,
M.Lewis.
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Ref.
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Proc Natl Acad Sci U S A, 1994,
91,
2517-2521.
[DOI no: ]
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PubMed id
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Note In the PDB file this reference is
annotated as "TO BE PUBLISHED".
The citation details given above were identified by an automated
search of PubMed on title and author
names, giving a
percentage match of
90%.
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Abstract
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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.
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