Tyr-179 and Lys-183 are essential for enzymatic activity of 11β-hydroxysteroid dehydrogenase

Jihad Obeid; Perrin C. White

doi:10.1016/0006-291X(92)92373-6

Tyr-179 and Lys-183 are essential for enzymatic activity of 11β-hydroxysteroid dehydrogenase

Jihad Obeid, Perrin C. White

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Abstract

Tyr-179 and Lys-183 are likely to be functionally important residues in 11β-hydroxysteroid dehydrogenase, as thease amino acids are absolutely conserved in all members of the "short chain dehydrogenase" family. We modified these residues by site-directed mutagenesis of rat cDNA and transfected these constructs into CHO cells. A highly but not absolutely conserved residue, Asp-110, was also studied. Mutation of Tyr-179 to Phe or Ser completely abolished enzymatic activity (interconversion of corticosterone and 11-dehydrocorticosterone), as did Lys-183→Arg. Asp-110→Asn affected activity only mildly. Tyr-179 and Lys-183 may be directly involved in the catalytic function of this class of enzymes.

Original language	English (US)
Pages (from-to)	222-227
Number of pages	6
Journal	Biochemical and Biophysical Research Communications
Volume	188
Issue number	1
DOIs	https://doi.org/10.1016/0006-291X(92)92373-6
State	Published - Oct 15 1992

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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@article{f34d7802210c4c0889dedbf943862f32,

title = "Tyr-179 and Lys-183 are essential for enzymatic activity of 11β-hydroxysteroid dehydrogenase",

abstract = "Tyr-179 and Lys-183 are likely to be functionally important residues in 11β-hydroxysteroid dehydrogenase, as thease amino acids are absolutely conserved in all members of the {"}short chain dehydrogenase{"} family. We modified these residues by site-directed mutagenesis of rat cDNA and transfected these constructs into CHO cells. A highly but not absolutely conserved residue, Asp-110, was also studied. Mutation of Tyr-179 to Phe or Ser completely abolished enzymatic activity (interconversion of corticosterone and 11-dehydrocorticosterone), as did Lys-183→Arg. Asp-110→Asn affected activity only mildly. Tyr-179 and Lys-183 may be directly involved in the catalytic function of this class of enzymes.",

author = "Jihad Obeid and White, {Perrin C.}",

note = "Funding Information: We thank Carl Monder for anti-l l-HSD serum and for helpful discussions, and Kathleen Cumow for reading the manuscript. J.O. is supported by National Research Service Award DK08715 and P.C.W. is an Irma Hirsch1 Trust Scholar. This work is supported by grants DK37094 and DK42169 from the National Institutes of Health, 6-609 from the March of Dimes, and by a grant from the Horace Goldsmith Foundation.",

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doi = "10.1016/0006-291X(92)92373-6",

language = "English (US)",

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T1 - Tyr-179 and Lys-183 are essential for enzymatic activity of 11β-hydroxysteroid dehydrogenase

AU - Obeid, Jihad

AU - White, Perrin C.

N1 - Funding Information: We thank Carl Monder for anti-l l-HSD serum and for helpful discussions, and Kathleen Cumow for reading the manuscript. J.O. is supported by National Research Service Award DK08715 and P.C.W. is an Irma Hirsch1 Trust Scholar. This work is supported by grants DK37094 and DK42169 from the National Institutes of Health, 6-609 from the March of Dimes, and by a grant from the Horace Goldsmith Foundation.

PY - 1992/10/15

Y1 - 1992/10/15

N2 - Tyr-179 and Lys-183 are likely to be functionally important residues in 11β-hydroxysteroid dehydrogenase, as thease amino acids are absolutely conserved in all members of the "short chain dehydrogenase" family. We modified these residues by site-directed mutagenesis of rat cDNA and transfected these constructs into CHO cells. A highly but not absolutely conserved residue, Asp-110, was also studied. Mutation of Tyr-179 to Phe or Ser completely abolished enzymatic activity (interconversion of corticosterone and 11-dehydrocorticosterone), as did Lys-183→Arg. Asp-110→Asn affected activity only mildly. Tyr-179 and Lys-183 may be directly involved in the catalytic function of this class of enzymes.

AB - Tyr-179 and Lys-183 are likely to be functionally important residues in 11β-hydroxysteroid dehydrogenase, as thease amino acids are absolutely conserved in all members of the "short chain dehydrogenase" family. We modified these residues by site-directed mutagenesis of rat cDNA and transfected these constructs into CHO cells. A highly but not absolutely conserved residue, Asp-110, was also studied. Mutation of Tyr-179 to Phe or Ser completely abolished enzymatic activity (interconversion of corticosterone and 11-dehydrocorticosterone), as did Lys-183→Arg. Asp-110→Asn affected activity only mildly. Tyr-179 and Lys-183 may be directly involved in the catalytic function of this class of enzymes.

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Tyr-179 and Lys-183 are essential for enzymatic activity of 11β-hydroxysteroid dehydrogenase

Abstract

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